Effects of systemic arterial blood pressure on the contractile force of a human hand muscle.

The effect of physiological changes in systemic blood pressure on the force output of working abductor pollicis (AP) muscle was studied in six normal subjects. Supramaximal tetanic stimulation at the ulnar nerve produced repeated isometric contractions at 1-s intervals. Force output declined gradually with time. During the train of contractions, subjects voluntarily contracted the knee extensors for 1 min; this raised systemic blood pressure by 29%. Force output from AP rose in parallel with blood pressure so that 18% of the contraction force lost through fatigue was recovered for each 10% increase in blood pressure. When blood pressure in the hand was kept constant despite the increased systemic pressure, force output did not rise. The results show that muscle performance is strongly affected by physiological changes in central blood pressure and suggest that sensory input concerning the adequacy of muscle performance exerts a feedback control over the increase in systemic blood pressure during muscular activity.

NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY24-36, reduces renal vasoconstrictor activity in anaesthetised dogs.

The actions of neuropeptide Y (NPY) at the autonomic neuroeffector junction have been attributed to two main receptor subtypes. At NPY Y1 receptors, located postsynaptically, NPY has been shown to produce vasoconstriction, or to potentiate the action of other vasoconstrictor agents. At NPY Y2 receptors, located presynaptically on nerve terminals, NPY inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we have used the specific NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY, which lacks local constrictor activity, and have demonstrated inhibition of nerve-evoked vasoconstriction in the renal circulation of anaesthetised dogs in a way that suggests an intra-renal regional specificity. Under control conditions stimulation of the renal sympathetic nerves over a range of frequencies (1-5 Hz) reduced renal vascular conductance and glomerular filtration rate (GFR). Following the injection of the selective NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY24-36, nerve-evoked reductions in renal conductance were reduced by over 45%. At the lowest stimulation frequencies, reduced vasoconstrictor activity was associated with a marked increase in GFR in the presence N-acetyl [Leu28,Leu31]NPY24-36. At both higher levels of stimulation N-acetyl [Leu28,Leu31]NPY24-36 significantly inhibited vasoconstrictor activity and attenuated the nerve-evoked reductions in GFR. Full recovery of both variables was observed 20 min after N-acetyl [Leu28,Leu31]NPY24-36 injection. N-acetyl [Leu28,Leu31]NPY24-36 produced a similar inhibition of renal vasoconstrictor activity when the renal nerves were left intact and activated reflexly. These results suggest that NPY can act via NPY Y2 receptors to inhibit sympathetic vasoconstrictor activity in the renal circulation of dogs. On the basis of the demonstrated dissociation of effects on vascular conductance and GFR, we suggest that this might result from a preferential action of the NPY Y2 agonist on sympathetic nerves supplying the afferent arteriole of the kidney.

Effects of muscle perfusion pressure on fatigue and systemic arterial pressure in human subjects.

The effects of changes in arterial perfusion across the physiological range on the fatigue of a working human hand muscle were studied in seven normal subjects. With the hand above heart level, subjects made repeated isometric contractions of the adductor pollicis muscle at 50% of maximal voluntary contraction in a 6-s on, 4-s off cycle. To assess fatigue, a maximal isometric twitch was elicited in each "off" period by electrical stimulation of the ulnar nerve. The experiment was repeated at least 2 days later with the hand at heart level. Five subjects showed faster fatigue with the arm elevated, and two subjects showed little difference in fatigue for the two conditions. Central blood pressure rose in proportion to fatigue for the subjects overall and returned quickly to its initial level afterwards. We conclude that human muscle fatigue can be increased by physiological reductions in perfusion pressure. Central blood pressure increases as the muscle fatigues, a response that may partially offset declining muscle performance.

Movement detection at the human big toe.

1. To be detected, movements of the interphalangeal joint of the big toe must be greater than at other joints. This poor acuity may arise because the anatomy of the foot and ankle results in poor coupling between the toe and the muscles that operate it. To vary this coupling, the effect of ankle position on proprioceptive acuity at the toe was measured. 2. We measured proprioceptive acuity at the toe with the ankle in different positions and found that ankle plantarflexion did improve acuity. This implies that, with the ankle at mid-range or dorsiflexed, toe movement is inadequately transferred to muscle fascicles. 3. To determine actual changes in fascicle length of the toe extensor, movements of extensor hallucis longus near the toe and at the muscle-tendon junction were measured during surgical exposure in one subject. Ankle position greatly affected movement transfer from toe to muscle-tendon junction: no tendon movement was transferred with the ankle dorsiflexed, but all movement was transferred with the ankle plantarflexed. 4. When the relationship between joint rotation and muscle fascicle length measured in vivo was used to express the smallest detectable movements of the toe as proportional changes in muscle fascicle length, these detectable changes were similar to those at all other limb joints. This suggests that change in muscle fascicle length is of major interest to the nervous system.

Inhibition of sympathetic cholinergic vasodilatation by a selective NPY Y2 receptor agonist in the gracilis muscle of anaesthetised dogs.

Neuropeptide Y (NPY) is known to be co-stored and co-released from sympathetic nerve terminals. In the cardiovascular system NPY acts on two main receptor subtypes. At the postjunctional or Y1 receptor NPY causes constriction directly in addition to potentiating other vasoconstrictor agents. NPY acting at the prejunctional, or Y2 receptor, inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we used the selective Y2 receptor agonist N-acetyl[Leu28,Leu31]NPY24-36 to examine the role of NPY in the modulation of sympathetic vascular control in skeletal muscle in anaesthetised dogs. No systemic pressor or local constrictor activity was observed in response to N-acetyl[Leu28, Leu31]NPY24-36 administration, therefore allowing us to examine the neuroinhibitory actions of NPY in the absence of direct vascular effects on blood flow. Stimulation of the sympathetic nerves to the gracilis muscle engages both sympathetic cholinergic and sympathetic adrenergic fibres and produces an initial vasodilatation followed by a slower vasoconstriction. Nerve evoked vasodilatation was inhibited by over 50% in the presence of the selective NPY Y2 agonist N-acetyl[Leu28,Leu31]NPY24-36. This dilatation was abolished by atropine, confirming its cholinergic nature. N-Acetyl[Leu28,Leu31]NPY24-36 was found to have no effect on nerve evoked vasoconstriction. The results demonstrate a NPY Y2-receptor mediated inhibition of nerve evoked sympathetic cholinergic vasodilatation but not of sympathetic vasoconstriction.

Post-exercise depression of baroreflex slowing of the heart in humans.

In normal human subjects, we tested whether a 20- to 30-min period of rhythmic exercise, intended to provoke strong activation of the sympathetic nerves, would lead to prolonged inhibition of vagally mediated bradycardia evoked reflexly by stimulation of the baroreceptors by neck suction. Negative pressure within the neck cuff (-40 to -80 mmHg) reflexly evoked a reproducible increase in pulse interval. Following exercise, this increase in pulse interval was reduced from 444 +/- 104 ms to 76 +/- 57 ms (mean +/- SEM). Recovery time was 42 +/- 9 min. These findings demonstrate a prolonged attenuation of cardiac vagal action following rhythmic exercise in normal human subjects. It is known that neuropeptide Y (NPY) is released from cardiovascular sympathetic nerves, that it attenuates cardiac vagal action and that plasma levels of NPY are elevated for a prolonged period after exercise. Therefore, it is proposed that NPY, released from sympathetic nerves during exercise, attenuates reflexly evoked cardiac vagal action for a prolonged period after exercise ends.

Effects of arterial perfusion pressure on force production in working human hand muscles.

1. The effects of hydrostatic changes in perfusion pressure on performance of working fatigue-resistant muscle fibres in the hand were studied in six normal subjects. 2. Supramaximal stimuli were delivered in trains of 200 ms duration, at 1 train S-1, to the ulnar nerve proximal to the wrist to produce isometric contractions of adductor pollicis. The force of contraction was measured and, after a level contraction force was achieved, the arm was passively raised or lowered. 3. Lifting the hand 45 cm above the heart produced a decline in force output from the muscle within several seconds which, after 4 min, fell by 22% below the steady-state level. Lowering the hand 45 cm below heart level produced an 8% increase in force output. Greater changes in force output occur at higher workloads. 4. It is concluded that in human subjects, muscle performance is sensitive to changes in perfusion pressure that occur across the physiological range. At moderate work levels, force output of the working muscles in the hand can vary by up to 30% over the physiological range of blood pressure. This dependence of muscular force on blood perfusion is of potential importance to motor control during normal activities.

Postural stability of the head in response to slowly imposed, small elastic loads.

To examine postural stability of the head, slow, undetectable rotations of small amplitude were imposed about a vertical axis while human subjects maintained a stationary body. Six normal subjects were used. The rotations were imposed through an elastic linkage, and lasted 4 s. The amplitude of head rotation was small, approximately 0.002 rad. The imposed perturbations commenced from an unloaded resting position with the head facing forward, under four conditions (1) relaxed, eyes closed; (2) relaxed, eyes open; (3) still, eyes closed; and (4) still, eyes open. The terms "relaxed' and "still' refer to the prior instructions given to the subjects regarding how they were to hold their head. There was a near linear relationship between average torque and average head angle. The effective stiffness of the head on the neck was notably low, approximately 10 Nm rad-1. Two-way analysis of variance (ANOVA) demonstrated ability to increase mean stiffness between "relaxed' and "still' conditions by 51% (P < 0.02). Visual input did not change mean stiffness significantly. Therefore, for the rotations to have been imperceptible, either the visual shifts involved must have been imperceptible, or the eyes must have counterrotated.

Selection of motor responses on the basis of unperceived stimuli.

In a previous study, the sensory phenomenon of "backward masking" was used to demonstrate that subjects can preprogram a single stereotyped voluntary movement or movement-sequence and that such a movement can be triggered in response to a stimulus that is not perceived (that is, a stimulus of which the subject is unaware). In the present study, visual stimuli were presented at random in one of two different locations to normal human subjects in a choice reaction-time (RT) task. When the stimulus appeared in one of the locations, subjects made a motor response. When the stimulus appeared in the other location, subjects made a different motor response. Large and small stimuli were presented in either location. In some trials, the small stimulus was followed 50 ms later by the large stimulus. The small stimulus was then "masked" by the large stimulus and could not be perceived on forced-choice testing. Despite not perceiving the test stimulus in either of its randomly selected locations, subjects were able to select and execute the motor response appropriate for each location. The RTs for responses to the masked stimulus and to the same stimulus presented without masking (and so, easily perceived) were the same. This result implies that appropriate programs for two separate movements can be simultaneously held ready for use, and that either one can be executed when triggered by specific stimuli without subjective awareness of such stimuli and so without further voluntary elaboration in response to such awareness.

Inhibition of vagally induced gastric contractions by sympathetic stimulation, neuropeptide Y and galanin.

The effects on vagally-induced gastric contractions of local electrical stimulation of the gastric sympathetic nerves were investigated in anaesthetised cats. Sympathetic stimulation caused an inhibition of vagally mediated gastric contractions which survived beta-adrenoceptor blockade and could not be mimicked by the alpha-adrenoceptor agonist phenylephrine. We therefore concluded that the inhibition was not predominantly dependent upon activation of alpha or beta adrenoceptors, although some effect attributable to noradrenaline could not be entirely excluded. In an attempt to determine the mechanism of this phenomenon, we administered exogenous neuropeptide Y (NPY) and galanin (GAL), both of which are known to occur as cotransmitters in some sympathetic nerves in the cat. Both NPY and GAL were able to mimic the effect of sympathetic stimulation on vagally-induced gastric contractions but their effects were variable.

Detection of movements imposed on human hip, knee, ankle and toe joints.

1. The angular displacements necessary for 70% correct detection were determined in normal subjects at the hip, knee and ankle joints, and the interphalangeal joint of the big toe. Angular velocities between 0.1 and 50 deg s-1 were tested. The hip and knee joints were tested in slight flexion and the ankle and toe joints were tested in the mid-range of the normal excursion. The joints were carefully supported for testing and the muscles acting at the joints were relaxed. 2. When detection thresholds and velocities were assessed in terms of angular displacements and angular velocities, proprioceptive performances at the hip, knee and ankle joints were superior to that at the toe joint. 3. When detection levels and displacement velocities were expressed in terms of linear displacements and velocities at the tip of the extended toe for all four joints, instead of in angular terms, the ankle gave the best performance and the hip and knee the worst. 4. The detection level and velocity data were expressed also in terms of proportional changes in the fascicle lengths of muscles operating these joints. Analysis in these terms showed that performance was similar at the hip, knee and ankle joints, but that performance for the toe was much poorer than for the other joints. 5. These results for the hip, knee and ankle are similar to those previously measured for the elbow and distal interphlangeal joint of the finger, and are consistent with the theory that muscle fascicle length is the variable of significance to the central nervous system. However, the proprioceptive performance at the big toe is notably poorer than all other joints studied and analysed in terms of this variable.

Stable human standing with lower-limb muscle afferents providing the only sensory input.

1. This study investigated the sources of sensory information upon which normal subjects' ability to stand depends. 2. An 'equivalent body' was used to simulate the physical properties of each subject's body during standing. The modulation of ankle torque required to support the equivalent body in an upright position was similar to that required to support the subject's own body when standing. However, when balancing the equivalent body, vestibular inputs were excluded from directing the appropriate changes in ankle torque. Thus, stability of stance could be studied with (normal stance) and without (balancing equivalent body) modulation by vestibular inputs. Vision could be excluded by closing the eyes. Sensory input from the feet and ankles could be removed by local anaesthesia from prolonged ischaemia, induced by occluding blood flow with inflated pneumatic cuffs just above the ankles. With vestibular, visual and peripheral sensory inputs negated, standing could rely only upon remaining sensory inputs, notably those from sensory receptors in the leg muscles. 3. Unlike the human body, the equivalent body used to negate vestibular inputs is not segmented. Therefore, the effects on stability of having a segmented body were determined by splinting subjects during standing so that only ankle movement was possible. This was done in the presence and absence of visual stabilization. 4. For each experimental task, either standing or balancing the equivalent body, sway was recorded while posture was unperturbed. Root mean square values of sway amplitude and power spectra were used to compare conditions. 5. Every subject could balance the equivalent body in a stable way when the eyes were closed, and when the feet were anaesthetized.(ABSTRACT TRUNCATED AT 250 WORDS)

Proprioceptive, visual and vestibular thresholds for the perception of sway during standing in humans.

1. Thresholds for the perception of postural sway induced by gentle perturbations were determined for five normal standing subjects. In this context we understand 'perception' to mean 'able to give a subjective report'. The thresholds for the perception of movements that were equivalent to sway in velocity and amplitude were determined when the available sensory input was limited to only one, or a pair, of the vestibular, visual, and proprioceptive systems. To examine vestibular inputs alone, vision was excluded and the whole body was moved with the ankles in a fixed position. To examine visual inputs alone, the body was kept stationary and a 'room' was moved around the subjects to simulate the relative visual-field movement that occurs during standing. To limit the available sensory input to proprioception from the legs, subjects were held stationary and balanced a load that was equivalent to their own body using their ankles. In this situation, perturbations were applied to the 'equivalent body' and these could only be perceived from the resulting ankle movements. Thresholds for perceiving ankle movements were also determined in the same posture, but with the leg muscles bearing no load. 2. The thresholds for the perception of sway during standing were very small, typically 0.003 rad at a velocity of 0.001 rad s-1, and even smaller movements were perceived as the mean velocity of the sway increased up to 0.003 rad s-1. No difference was found between the thresholds for perceiving forward sway and backward sway. Eye closure during standing did not affect the threshold for perceiving sway. 3. When sensory input was limited to proprioception from the legs, the thresholds for the perception of passive ankle movements were equivalent to the thresholds for the perception of sway during standing with all sensory inputs available. When the leg muscles were relaxed, the thresholds for perceiving ankle movements increased approximately twofold. 4. The visual thresholds for perceiving movement were higher than the proprioceptive thresholds at slower velocities of movement, but there was no difference at higher velocities. 5. Both the proprioceptive and visual thresholds were sufficiently small to allow perception of the sway that was recorded when the subjects stood normally in a relaxed manner. In contrast, the vestibular thresholds were an order of magnitude greater than the visual or proprioceptive thresholds and above the largest sway movements that were recorded during normal standing.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional effects of a family of galanin antagonists on the cardiovascular system in anaesthetised cats.

Previous studies have shown that injection of galanin (GAL: 6.2 nmol/kg) causes prolonged inhibition of cardiac vagal action in anaesthetised cats. Stimulation of the cardiac sympathetic nerve (16 Hz for 5 min) also produces inhibition of cardiac vagal action, an effect which has been proposed to be due to the release of endogenous GAL from sympathetic nerves. In a previous study we tested galantide (M15) and in this study we compared galantide with two other GAL antagonists for their GAL antagonist activity in our experimental model. Each of these incorporate the N-terminal fragment GAL 1-13 and a C-terminal portion of another bioactive peptide and all are C-terminally amidated. GAL 1-13 Substance P 5-11 amide (galantide: M15: 62 nmol/kg and 156 nmol/kg), GAL 1-13 Spantide amide (C7: 156 nmol/kg) and GAL 1-13 NPY 24-36 amide (M32a: 62 nmol/kg) all significantly reduced the cardiac vagal inhibitory effect of exogenous GAL and also reduced the effect of sympathetic stimulation on subsequent cardiac vagal slowing, giving strong support to our hypothesis that GAL is involved in this phenomenon. No antagonist reduced the depressor effect of GAL. This study demonstrates the GAL antagonist properties of these agents on autonomic neuroeffector functions making them useful tools in elucidating further functions of endogenous GAL.

The role of sensory information in the guidance of voluntary movement: reflections on a symposium held at the 22nd annual meeting of the Society for Neuroscience.

This article reviews a symposium on the sensory control of movement held at the 22nd annual meeting of the Society for Neuroscience. Four speakers addressed a large audience on the proposition that "one can only control what one senses." Charles Vierck supported the notion with a description of the severe motor deficits caused by lesions of the spinal dorsal columns (DCs) in monkeys. In the discussion of Vierck's presentation, Robert Forget described the difficulties experienced by deafferented patients in tasks of daily life. Next, John Brooke showed that sensorimotor transformations vary greatly with task, anticipation, and uncertainty. In light of this, he questioned the simplifications inherent in servo and equilibrium-point theories of motor control. Paul Cordo then showed that in a rapid throwing task, proprioceptive information is used to control the moment of release (contradicting the idea that sensory feedback is too delayed for ballistic movements). Dick Burgess, like Brooke, criticized equilibrium-point models; he argued that a subject's sense of effort is a measure of the internal motor command, which should correspond to specific equilibrium points. However, his experimental data were inconsistent with this interpretation. He suggested instead that motor output is adjusted by comparing incoming afferent information to an expected "afferent template." Anatol Feldman and Mark Latash disagreed, saying that a constant sense of effort does not imply a constant equilibrium-point command. The equilibrium-point debate was not resolved, but the symposium ended with a consensus that in most motor tasks, one can control only what one senses.

Desensitization by neuropeptide Y of effects of sympathetic stimulation on cardiac vagal action in anaesthetised dogs.

The effects of a long-lasting intravenous infusion of neuropeptide Y (NPY, 180 +/- 8 min, 53 +/- 4 micrograms/kg/h) on the prolonged inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation and bolus intravenous injections of NPY were investigated in anaesthetised dogs. Sympathetic stimulation and NPY injection were performed on four separate occasions; once in control conditions, then once early and again late in the period of NPY infusion, and then on a final occasion 60-90 min after the cessation of NPY infusion. The maximum inhibition of cardiac vagal action evoked by an injection of NPY was significantly less late in the NPY infusion when compared with the other three injection groups (ANOVA, P < 0.001). Also the time to half-recovery of this response was significantly less than that seen in the other three injection groups (ANOVA, P < 0.001). The maximum inhibition of cardiac vagal action evoked by sympathetic stimulation was significantly reduced late in the NPY infusion when compared with the other three stimulation groups (ANOVA, P < 0.0001). The time for half-recovery of this response was also less than that of the other three stimulation groups (ANOVA, P < 0.001). The results indicate that desensitisation of the vagal attenuation to both exogenous NPY and sympathetic stimulation occurred during a long-lasting period of NPY infusion. This is consistent with the proposal that NPY is a mediator of this sympathetic-evoked vagal attenuation.

Galanin antagonist effects on cardiac vagal inhibitory actions of sympathetic stimulation in anaesthetized cats and dogs.

1. Galantide, a putative galanin antagonist composed of twenty amino acids, caused a significant reduction in the vagal attenuating action of galanin injection (20 micrograms/kg; 6.2 nmol/kg) in anaesthetized cats at both ten times (137 micrograms/kg; 62 nmol/kg) and twenty-five times (343 micrograms/kg: 156 nmol/kg) the molar dose of galanin. Galantide did not block the depressor action of galanin in these animals. 2. Galantide, at both doses, also significantly reduced the vagal attenuating action of a 5 min period of cardiac sympathetic stimulation at 16 Hz in anaesthetized cats. 3. In anaesthetized dogs, galantide, at the same dose used in cats (137 micrograms/kg; 62 nmol/kg) had no significant effect on the vagal attenuation evoked by cardiac sympathetic stimulation or injection of neuropeptide Y (35 micrograms/kg; 8.2 nmol/kg). 4. This study therefore demonstrates antagonist properties of galantide on the vagal inhibitory action of galanin. It supports the hypothesis that the vagal inhibitory factor released by cardiac sympathetic nerve stimulation in the cat, but not the dog, is galanin, although it does not exclude the possibility of other factors playing a more minor role. Because galantide was not shown to block the depressor action of galanin, this study also suggests that there may be more than one galanin receptor subtype.

Pharmacological separation of cardio-accelerator and vagal inhibitory capacities of sympathetic nerves.

Prolonged attenuation of vagal action at the heart, proposed to be due to release of the sympathetic cotransmitter neuropeptide Y (NPY), follows stimulation of cardiac sympathetic nerves. It has been shown that pretreatment with reserpine depletes cardiac and neuronal stores of both noradrenaline and NPY, while combined pretreatment with reserpine and the ganglion blocking agent chlorisondamine reduces depletion of NPY, while still depleting noradrenaline. The effects of reserpine pretreatment and combined chlorisondamine and reserpine pretreatment on the inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation (16 Hz, 2 min) were compared in anaesthetised dogs. In dogs with no pretreatment (n = 6), sympathetic stimulation evoked an immediate cardio-acceleration, and a prolonged inhibition of cardiac vagal action, with a maximum percent inhibition (MPI) and time to half-recovery (T50) of 78 +/- 6% and 16 +/- 2 min respectively. In dogs pretreated with reserpine (n = 6, 1 mg/kg, 24 h), the immediate cardio-acceleration (ANOVA, P < 0.01), and the magnitude (MPI = 31.8%, ANOVA, P < 0.001) and duration (T50 = 6 +/- 1 min, ANOVA, P < 0.05) of inhibition of cardiac vagal action following sympathetic stimulation were significantly attenuated. In dogs with combined chlorisondamine (n = 5, 2 mg/kg, 48 and 24 h) and reserpine pretreatment, there was again significantly reduced cardio-acceleration (ANOVA, P < 0.01), but the inhibition of cardiac vagal action following sympathetic stimulation did not significantly differ from untreated animals (MPI = 79 +/- 8%, T50 = 21 +/- 6 min). Intravenous injections of NPY (25-50 micrograms/kg) evoked prolonged inhibition of cardiac vagal action in untreated and both groups of pretreated animals. These experiments indicate that the cardio-accelerator and vagal inhibitory capacities of sympathetic nerve stimulation can be separated, and are consistent with the sympathetic vagal inhibitory factor being NPY.

The effects of galanin and galanin fragments on cardiac-vagal action and blood pressure in the anaesthetised cat.

Galanin (GAL), 29 amino acid peptide, has previously been shown to inhibit cardiac vagal action, and to cause a fall in systemic blood pressure in anaesthetised cats, at a dose of 6.2 nmol/kg. Here, the biological activity of exogenous GAL fragments was assessed in anaesthetised cats. GAL 1-16 at a dose equimolar with the full GAL 1-29 peptide (6.2 nmol/kg) and at a dose five times the molar dose of GAL 1-29 (31 nmol/kg), was found to be biologically active although the effects were less than that of the full peptide. GAL 1-15 at doses up to 10-times the molar dose of GAL 1-29, however, was not active, suggesting that amino acid 16, isoleucine, is critical for activity. In addition, GAL 15-29 and 21-29 showed no biological activity at doses up to 10-times the molar dose of GAL 1-29. These results suggest that the N-terminal rather than the C-terminal end of the GAL molecule is the one responsible for most of GAL's biological activity in this preparation.

Inhibition of cardiac vagal action by galanin but not neuropeptide Y in the brush-tailed possum Trichosurus vulpecula.

1. Stimulation of the right cardiac sympathetic nerve for 2 min at 16 Hz in the presence of either beta- or alpha- and beta-adrenoceptor blockade evoked attenuation of cardiac vagal action in eight possums: 31.3 +/- 10.3% maximum inhibition of cardiac vagal action on prolonging pulse interval, with a time to half-recovery of 4.9 +/- 1.1 min. 2. Intravenous injection of galanin (2-3.5 nmol kg-1) evoked similar inhibition of cardiac vagal action: 41.3 +/- 4.1% maximum inhibition of cardiac vagal action on pulse interval, with a time to half-recovery of 13.4 +/- 2.3 min. 3. Intravenous injection of neuropeptide Y (NPY) at greater molar doses (6.5-10 nmol kg-1) caused no inhibition of cardiac vagal action. 4. The galanin injections caused a powerful pressor response: 57.1 +/- 4.9 mmHg increase in systolic blood pressure. NPY caused a smaller pressor response, despite administration of higher molar doses: 36.7 +/- 3.0 mmHg increase in systolic blood pressure. 5. In the possum, galanin but not NPY can mimic the effects of cardiac sympathetic nerve stimulation on vagal action. Galanin also causes large pressor effects.