Bacterial swarming: a biochemical time-resolved FTIR-ATR study of Proteus mirabilis swarm-cell differentiation.

Fourier transform infrared spectroscopy was applied to the study of the differentiation process undergone by Proteus mirabilis. This bacterium exhibits a remarkable dimorphism, allowing the cells to migrate on a solid substratum in a concerted manner yielding characteristic ring patterns. We performed an in situ noninvasive analysis of biochemical events occurring as vegetative cells differentiate into elongated, multinucleate, nonseptate, and hyperflagellated swarm cells. The major findings arising from this study are (i) the real-time monitoring of flagellar filament assembly, (ii) the evidence for de novo synthesis of qualitatively different lipopolysaccharides (LPS) and/or exopolysaccharides (EPS) constituting the slime into which bacteria swarm, and (iii) the alteration in the membrane fatty acid composition with a concomitant 10 degrees C decrease in the gel/liquid crystal phase transition resulting in an elevated membrane fluidity in swarm cells at the growth temperature. The time course of events shows that the EPS-LPS syntheses are synchronous with membrane fatty acid alterations and occur about 1 h before massive flagellar filament assembly is detected. This study not only provided a time sketch of biochemical events involved in the differentiation process but also led to the identification of the major spectral markers of both vegetative and swarm cells. This identification will allow to resolve the time-space structure of P. mirabilis colonies by using infrared microscopy.

Ruptures utérines à la maternité du Centre Hospitalier National Yalgado Ouedraogo (CHN-YO): Aspects épidémiologiques et cliniques

Une étude rétrospective sur 10 ans (du 1er janvier 1980au 31 décembre 1989) à la maternité du Centre Hospi-talier National Yalgado Ouédraogo à partir de 369 dos-siers cliniques a montré que les ruptures utérines re s -tent fréquentes avec une rupture utérine pour 76 accou-chements. Cette affection intéresse les femmes jeunesavec un maximum entre 21 et 30 ans.Dans les antécédents de ces patientes il faut retenir lamulti-parité, les césariennes antérieures et le non suivides grossesses

Stress-induced enhancement of colitis in rats: CRF and arginine vasopressin are not involved.

Because exacerbation of colitis seems to be associated with stress, we proposed evaluating the influence of stress and the involvement of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on experimental colitis in rats. Partial restraint stress was applied during 4 consecutive days, before or after intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNB) instillation (15 mg) in rats. Finally, two groups of rats were centrally injected with alpha-helical CRF-(9-41) (5 micrograms) or AVP antagonist (5 micrograms) before each session of stress. Stress was applied before or right after TNB enhanced colitis, with an increase in macroscopic and histological scores and myeloperoxidase activity, alpha-Helical CRF-(9-41) or AVP antagonist had no effect on TNB-induced colitis but enhanced the effects of stress on colitis. These results show that stress may exacerbate experimental colitis in rats and that CRF and AVP are not responsible for this effect.

Stress-induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells.

BACKGROUND: Psychological factors have long been implicated in the aetiology of irritable bowel syndrome often associated with abdominal pain. This work was designed to study, in rats, the influence of partial restraint stress on the abdominal cramps induced by rectal distension and to determine the role of corticotropin releasing factor (CRF) and mast cells degranulation in this response. METHODS: Abdominal contractions were electromyographically recorded. Thirty minutes after stress or intracerebroventricular CRF, rectal distension was performed by inflation of a balloon (0.4-1.2 mL). alpha-helical CRF9-41 or doxantrazole were administered centrally (15 min) and intraperitoneally (30 min), respectively, before stress. Histamine release and the number of mast cells were determined in colonic pieces from stressed and control rats. RESULTS: Stress and CRF enhanced the number of abdominal cramps evoked by rectal distension without affecting rectal compliance. alpha-helical CRF9-41 and doxantrazole antagonized the stress and CRF-induced enhancement of abdominal cramps. Stress increased the colonic histamine content whereas the number of colonic mast cells was unchanged. CONCLUSIONS: Stress enhances abdominal contractions in response to rectal distension in rats via pathways involving central CRF and intestinal mast cells.

Reversal by NPY, PYY and 3-36 molecular forms of NPY and PYY of intracisternal CRF-induced inhibition of gastric acid secretion in rats.

1. The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion was studied in urethane-anaesthetized rats by use of peptides with various selectivity for Y1, Y2 and Y3 subtypes: NPY, a Y1, Y2 and Y3 agonist, peptide YY (PYY), a Y1 and Y2 agonist, [Leu31, Pro34]-NPY, a Y1 and Y3 agonist, NPY(3-36) and PYY(3-36), highly selective Y2 agonists and NPY(13-36) a weak Y2 and Y3 agonist. Peptides were injected intracisternally 10 min before intracisternal injection of CRF (10 micrograms) and gastric acid secretion was measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10 micrograms kg-1 h-1, i.v.) infusion which started 10 min after CRF injection. 2. Intracisternal injection of CRF (10 micrograms) inhibited by 56% gastric acid secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY (0.1-0.5 microgram) did not influence the acid response to pentagastrin but blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3-36) (0.5 microgram) and PYY(3-36) (0.25 and 0.5 microgram) also completely blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion. 3. [Leu31, Pro34]-NPY (0.5-5 micrograms) and NPY(13-36) (0.5-5 micrograms) injected intracisternally did not modify gastric acid secretion induced by pentagastrin or CRF inhibitory action. 4. The sigma antagonist, BMY 14802 (1 mg kg-1, s.c.) did not influence the acid response to pentagastrin but prevented the antagonism by PYY(3-36) (0.5 microgram) of the CRF antisecretory effect. 5. These results show that both PYY and NPY and the 3-36 forms of PYY and NPY are equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated gastric acid secretion. The structure-activity profile suggests a mediation through Y2 receptor subtype and the involvement of sigma binding sites.

Interaction between CCK and opioids in the modulation of the rectocolonic inhibitory reflex in rats.

The effects of cholecystokinin octapeptide (CCK-8) as well as the involvement of opioid system were evaluated in rectal distension (RD)-induced colonic motor inhibition in rats. Rats were surgically prepared with electrodes implanted on the proximal colon, and a catheter was implanted in lateral ventricle of the brain. RD was performed by inflation (0.0-1.6 ml) of a balloon rectally inserted. RD 1.6 ml of induced an inhibition of the colonic spike bursts (3.1 +/- 0.5 per 5 min vs. 8.1 +/- 0.4 before RD). Intracerebroventricular but not intravenous injection of CCK-8 and A-71623 (50 and 100 ng/kg) reduced the RD-induced colonic motor inhibition, whereas A-63387 was ineffective. PD-135,158 (10 micrograms/kg icv) suppressed the inhibitory reflex caused by RD. Devazepide (100 micrograms/kg icv) had no effect in this reflex function. Devazepide (1 microgram/kg), naloxone (0.1 mg/kg), and nor-binaltorphimine (nor-BNI; 10 mg/kg) reversed the blocking effect of CCK-8, whereas PD-135,158 (0.1 microgram/kg) and naltrindole (1 mg/kg) have no effect. In conclusion, CCK-8 acts on central alimentary cholecystokinin receptors to modulate the RD-induced inhibition of colonic motility through pathways involving activation of endogenous kappa-receptors.

The kappa agonist fedotozine modulates colonic distention-induced inhibition of gastric motility and emptying in dogs.

BACKGROUND/AIMS: Gastric motor disturbances, associated with a delay in gastric emptying, occur in patients with the irritable bowel syndrome. The influence of fedotozine and kappa agonists on the cologastric reflex produced by nonpainful colonic distention was evaluated in conscious dogs. METHODS: Colonic distention was applied in dogs fitted with either strain gauges or gastric cannula to assess its influence on gastrointestinal motility and gastric emptying, respectively. RESULTS: Colonic distention delayed the occurrence of gastric migrating motor complex by 141%, an effect blocked by intravenous fedotozine, U 50,488 (25 and 50 micrograms/kg), and hexamethonium (0.5 mg/kg) but not by D-Ala2, N-methyl, Phe4, Gly5-ol enkephalin (1, 5, and 10 micrograms/kg), granisetron (50 and 100 micrograms/kg), or bretylium tosylate (5 mg/kg). Nor-binaltorphimine hydrochloride (1 mg/kg intravenously) eliminated the suppressive action of fedotozine. Colonic distention reduced the 1-hour gastric emptying of solids by 40.1%, an effect blocked by fedotozine and U 50,488 (50 and 100 micrograms/kg); nor-binaltorphimine hydrochloride (1 mg/kg) antagonized the blocking effect of fedotozine. CONCLUSIONS: Fedotozine acts through kappa receptors to block the colonic distention-induced delay on gastric motility and emptying. The cologastric reflex involves nicotinic ganglionic receptors but not adrenergic pathway and 5-hydroxytryptamine 3 receptors.

Cholecystokinin blockade of emotional stress- and CRF-induced colonic motor alterations in rats: role of the amygdala.

Intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) and emotional stress (ES) induce stimulation of colonic motility in rats, an effect blocked by i.c.v. injection of CCK-8s. This study examined in rats the contribution of the central nucleus of the amygdala (CA) in the blocking effect of CCK-8s on ES and CRF-induced colonic hypermotility. CRF (500 ng/kg, i.c.v.) induced a 73.5% increase in colonic spike burst frequency. Bilateral infusions of 1, 5, 10 and 20 ng/kg of CCK-8s in the CA region 10 min prior to CRF i.c.v. injection reduced, in a dose related manner, the CRF-induced stimulation of colonic motility. A 109% increase in colonic spike burst frequency was observed in rats placed in a test cage in which they had previously received electric footshocks (ES). CCK-8s and A-71623, a selective CCK-A receptor agonist, (10, 25 and 50 ng/kg) infused bilaterally into the CA, 30 min before ES, significantly reduced this stimulatory effect, while CCK-4 and A-63387, a selective CCK-B receptor agonist (10, 25 and 50 ng/kg), had no effect on such a response. CA lesions by ibotenic acid did not affect ES-induced increase in colonic spike activity. However, CCK-8s (50 ng/kg) microinfused into CA lesioned rats was unable to block the ES-induced stimulation of colonic motility, while CCK-8s i.c.v. injected (100 ng/kg) is still active on the colonic response to ES. These results suggest that CA is a site of interaction of CCK-8s with CRF to block the colonic response to stress and that these effects involve the CCK-A receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of CRF- and dopamine-induced stimulation of colonic motility by CCK and igmesine (JO 1784) in the rat.

1. The role of dopamine in the genesis of corticotropin releasing factor (CRF)- and emotional stress (ES)-induced stimulation of colonic motility, as well as the mechanism of antagonistic action of cholecystokinin octapeptide (CCK-8s) and igmesine (alpha sigma receptor ligand, formerly JO 1784) on dopamine-induced colonic hypermotility, have been investigated in the rat. 2. ES and i.c.v. injection of CRF (0.5 microgram kg-1) increased the frequency of colonic spike bursts by 63% and 114%, respectively. Prior i.c.v. administration of (+)-SCH 23390 (a D1 receptor antagonist, 10 micrograms kg-1) significantly (P < 0.05) reduced the CRF- and ES-induced increase in colonic spike burst; whereas, sulpiride (a D2 receptor antagonist, 10 micrograms kg-1) blocked the CRF-induced stimulation of colonic spike bursts but had no effect on the colonic response to stress. 3. I.c.v. injection of dopamine (100 micrograms kg-1), increased colonic spike burst frequency by 54%. (+)-SKF 38393 (5 micrograms kg-1), a selective D1 receptor agonist, and quinpirole (5 micrograms kg-1), a selective D2 receptor agonist, increased colonic spike burst frequency by 71% and 70% respectively. CCK-8s (0.1 microgram kg-1) and igmesine (0.1 microgram kg-1) injected i.c.v. completely prevented the stimulatory effects of dopamine, (+)-SKF 38393 and quinpirole. 4. Previous i.c.v. injection of devazepide, a CCKA receptor antagonist, (10 micrograms kg-1) antagonized the inhibitory effects of both CCK-8s and igmesine injected i.c.v. on dopamine-induced colonic hyperkinesia. 5. These results show that CRF stimulates colonic motility through activation of central dopaminergic mechanisms in response to stress; furthermore, CCK-8s inhibits dopamine-induced colonic hyperkinesia through a mechanism involving D1 and D2 receptors. The sigma receptor ligand igmesine, blocks the CRF and ES-induced colonic hyperactivity via an interaction with central CCK mechanisms.

Comparative involvement of 5-HT1, 5-HT2 and 5-HT3 receptors in stress-induced colonic motor alterations in rats.

The role of 5-HT1, 5-HT2 and 5-HT3 receptors in the genesis of colonic motor alterations induced by emotional stress was evaluated in rats equipped with implanted nickel/chrome electrodes on the proximal colon and a catheter into the lateral ventricle of the brain. In control rats the frequency of colonic spike bursts increased from 7.6 +/- 1.3 to 16.8 +/- 1.3 per 10 min when the rats were placed in a test cage in which they had previously received electric footshocks. I.p. injection of methysergide (0.1 mg/kg) reduced by 54% the emotional stress-induced increase of colonic spike burst frequency, while a higher dosage (1 mg/kg) of methysergide had no effect. The i.p. injection of ketanserin (a 5-HT2 receptor antagonist, 0.1 and 1 mg/kg) or granisetron (a 5-HT3 receptor antagonist, 0.1 and 1 mg/kg) had no effect on emotional stress-induced colonic hyperkinesia. The i.p. injection of the 5-HT1A receptor agonists, buspirone (1 mg/kg) or 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino(tetralin) (0.05 and 0.1 mg/kg) or benzodiazepine (clonazepam, 1 mg/kg) significantly reduced or suppressed the emotional stress-induced increase of colonic spike bursts. Injected i.c.v., buspirone, but not 8-OH-DPAT, also reduced the emotional stress-induced hyperkinesia. Pretreatment with devazepide receptor (1 microgram/kg) antagonized the inhibitory effects of buspirone and 8-OH-DPAT injected i.p. on emotional stress-induced colonic hyperkinesia but did not alter the effects of clonazepam (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Central neuropeptide Y and the sigma ligand, JO 1784, reverse corticotropin-releasing factor-induced inhibition of gastric acid secretion in rats.

1. The central interactions between the sigma ligand, JO 1784, [(+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethylbut-3- en-1-ylamine hydrochloride], or neuropeptide Y (NPY) and corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion were investigated in rats anaesthetized with urethane. Drugs were injected intracisternally (i.c.) or into specific hypothalamic nuclei. Gastric acid secretion was measured by the flushed technique under basal and pentagastrin (10 micrograms kg-1 h-1, i.v.) stimulated conditions. 2. Intracisternal injection of CRF (10 micrograms), bombesin (0.1 microgram) and human recombinant interleukin-1 beta (hIL-1 beta, 0.1 microgram) inhibited gastric acid response to pentagastrin by 72%, 56% and 62%, respectively. NPY (0.5 microgram) or JO 1784 (0.5 microgram) injected i.c. did not alter acid secretion but completely prevented the inhibitory effect of CRF. The antagonistic effect of NPY and JO 1784 against CRF was dose-related (0.01-0.5 microgram) and peptide-specific since NPY and JO 1784 did not alter the antisecretory action of bombesin or hIL-1 beta. 3. The putative sigma receptor antagonist, BMY 14802, (1 mg kg-1, s.c.) did not influence pentagastrin-stimulated acid secretion nor CRF-induced inhibition of gastric acid secretion; however, BMY 14802 administered s.c. 20 min before JO 1784 or NPY, abolished the antagonistic effect of both JO 1784 and NPY. 4. CRF (3 micrograms) microinjected into the hypothalamic paraventricular nucleus (PVN) and the lateral hypothalamus (LH) inhibited pentagastrin-stimulated gastric acid secretion by 61% and 51%; NPY (0.03 micrograms) or JO 1784 (0.03 micrograms) microinjected into the PVN had no effect by themselves but blocked CRF antisecretory action.There were more VPBs (220 +/- 75), a higher incidence of VT (60%) and more episodes of VT (11.5 +/- 6.0 compared to 0.7 +/- 0.3 episodes in the preconditioned dogs not given L-NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of inhomogeneity which resulted from preconditioning was abolished by L-NAME administration.5. L-NAME itself elevated blood pressure (from 96 +/- 5 mmHg diastolic to 119 +/- 7 mmHg), reduced heart rate (from 155 +/- 7 to 144 +/- 4 beats min-') but did not change LVEDP, LVdP/dt,,,,, coronary blood flow, ST-segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, L-NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 +/- 4.7 episodes per dog).6. It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.

Involvement of central dopamine and D1 receptors in stress-induced colonic motor alterations in rats.

The role of central versus peripheral influence of dopamine (DA) in the genesis of emotional stress (ES) induced by fear to receive electric footshocks on colonic motility was evaluated in rats equipped with implanted electrodes on the proximal colon. In control rats, the frequency of colonic spike bursts increased from 7.5 +/- 1.9 to 16.0 +/- 2.1 per 10 min when the rats were placed in a test box where they had previously received electric footshocks. This increase induced by ES was significantly p less than 0.05, reduced by previous ICV or IP administration of (+)SCH 23390 (a D1 receptor antagonist) at doses of 10 and 100 micrograms/Kg, respectively. Although sulpiride (a D2 antagonist) injected ICV or IP at similar doses had no effect on the ES-induced increase in the frequency of colonic spike bursts. DA (100 micrograms/kg), and the selective D1 (SKF 38383) or D2 (quinpirole) receptor agonist injected ICV at a dose of 5 micrograms/kg also increased significantly by 48.7, 54.8, and 68.7%, respectively, the colonic spike burst frequency whereas they are inactive when injected IP at similar and higher doses. These results suggest that, in rats, (a) emotional stress stimulates colonic motility through the stimulation of dopaminergic neurons involving D1 receptors and (b) exogenous activation of central D1 and D2 receptors similarly stimulate colonic motility by increasing the occurrence of colonic spike bursts.

Neuropeptide Y and sigma ligand (JO 1784) suppress stress-induced colonic motor disturbances in rats through sigma and cholecystokinin receptors.

The effects of neuropeptide Y (NPY), sigma ligand (JO 1784) and sulfated cholecystokinin octapeptide (CCK8s) on emotional stress (ES) and corticotropin-releasing hormone (CRH)-induced colonic hypermotility were evaluated in rats equipped with chronically implanted electrodes on the colon and a small catheter into the lateral ventricle of the brain. A 139% (97-172%) increase in colonic spike burst frequency was observed in rats placed in a test cage in which they had previously received electric footshocks, an event assimilated to an ES. Intracerebroventricular injection of CRH (0.5 microgram/kg) mimicked the effects of ES by increasing colonic spike burst frequency by 89.0%. Given i.c.v., both JO 1784 (0.1 microgram/kg) and NPY (0.15 microgram/kg) blocked these stimulatory effects. Similarly, i.c.v. administration of CCK8s (0.1 microgram/kg) abolished both ES and CRH stimulated colonic motility, an effect reproduced by central injection of JMV 180, a cholecystokinin (CCK) derivative with high affinity for CCKA receptors, (1 microgram/kg), but not by JMV 170, a CCK derivative with low affinity for CCKA receptor at similar or higher dose. BMY 14802 (a sigma receptor antagonist) injected s.c. (1 mg/kg) abolished the antagonistic effects of JO 1784 and NPY on the ES-induced colonic hyperkinesia. Injected i.c.v., devazepide (L 364,718), a CCKA receptor antagonist, at 0.1 and 1 microgram/kg, abolished the effect of both JO 1784 and NPY; by contrast L365,260, a CCKB antagonist, required a dose of 10 micrograms/kg to block the antagonistic effect of NPY and JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS)

CNS vasopressin mediates emotional stress and CRH-induced colonic motor alterations in rats.

The effects of emotional stress (ES) corresponding to conditioned fear on colonic motility and its antagonism by [deamino-Pen1, Val4, D-Arg8]vasopressin, a vasopressin antagonist, were investigated by electromyography in conscious fasted rats fitted with chronically implanted electrodes. A 117% increase (19.6 +/- 2.1 vs. 9.0 +/- 0.9 cycles/10 min during the control period) in the frequency of colonic spike bursts was observed when rats were placed for 30 min in a box in which they had previously received electric foot shocks. Intracerebroventricular (icv) administration of corticotropin-releasing hormone (CRH; 0.5 micrograms/kg) mimicked the effects of ES and increased the spike burst frequency of the colon by 88.6% from 5 to 15 min after its administration. At doses between 5 and 20 micrograms/kg the antagonist [deamino-Pen1, Val4, D-Arg8]vasopressin significantly reduced or abolished the effects of ES and CRH administration on colonic motility. Injected icv at doses of 2.5 and 5 ng/kg [Arg8]vasopressin dose dependently increased the frequency of colonic spike bursts. These effects were not reproduced by similar or higher (50 ng/kg) doses given intraperitoneally, and the effects were abolished after previous administration of vasopressin at a dose of 20 micrograms/kg. It is concluded that the effects of ES on colonic motility in rats previously shown to be linked to the central nervous system (CNS) release of CRH are in turn mediated through the central release of vasopressin.

Neuropeptide Y and sigma ligand (JO 1784) act through a Gi protein to block the psychological stress and corticotropin-releasing factor-induced colonic motor activation in rats.

The effects of neuropeptide Y and sigma ligands (d-NANM and JO 1784) on corticotropin-releasing factor (CRF) and psychological stress-stimulated caecal and colonic motility were evaluated by electromyography in rats equipped with chronically implanted electrodes on the caecum and proximal colon and a small catheter into the right lateral ventricle of the brain. Exposure to a psychological stress for 30 min increased significantly (P less than 0.05) the frequency of caecal and colonic spike bursts, an effect which was mimicked by intracerebroventricular administration of CRF (300 ng/kg). Injected intracerebroventricularly, 30 min prior to the psychological stress or intracerebroventricular administration of CRF, neuropeptide Y (150 ng/kg) abolished the excitatory effect on caeco-colonic motility. Similarly, prior administration of d-NANM (100 ng/kg) and JO 1784 (50 ng/kg) abolished the caeco-colonic hypermotility induced by psychological stress and intracerebroventricular injection of CRF. Four days after intracerebroventricular administration of pertussis toxin (150 ng/kg), both neuropeptide Y and JO 1784, when administered centrally, were unable to antagonize the stress-induced hyperkinesia. It is concluded that central administration of neuropeptide Y and sigma ligands abolish the stimulatory effects of psychological stress on caeco-colonic motility by blocking the pathways by which CRF activates the motility, through a common mechanism involving a pertussis toxin-sensitive Gi protein.

Brain CCKA receptors mediate the colonic motor response to feeding in dogs.

The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10 micrograms/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCKA receptors.

Conditioned emotional response in rats enhances colonic motility through the central release of corticotropin-releasing factor.

The effect of a mental stress model corresponding to conditioned fear on cecocolonic motility was evaluated electromyographically in intact and hypophysectomized rats equipped with electrodes implanted in the cecum and proximal colon over a long period and a small polyethylene catheter inserted into the right lateral ventricle of the brain. Intact fasted and fed rats showed an increase of 82.3% and 67.2%, respectively, in colonic spike-burst frequency when placed for 30 minutes in a box in which they had previously received electrical shocks in their feet. Intracerebroventricular administration of corticotropin-releasing factor (0.5 micrograms/kg) mimicked the effects of mental stress and increased cecocolonic spike-burst frequency by 75.8%. The specific corticotropin-releasing factor receptor antagonist alpha-helical CRF9-41 given intracerebroventricularly (5 micrograms/kg) prevented both the effects of mental stress and corticotropin-releasing factor (0.5 micrograms/kg intracerebroventricularly) on colonic spike-burst frequency. In contrast, diazepam (0.5 mg/kg IM) suppressed colonic hypermotility induced by mental stress but not that resulting from intracerebroventricular injection of corticotropin-releasing factor (0.5 micrograms/kg). Increased colonic spike-burst frequency induced either by stress or by central administration of corticotropin-releasing factor was not prevented by hypophysectomy. It was concluded that mental stress increases the frequency of cecocolonic spike-burst activity and that these effects are related to the central release of corticotropin-releasing factor because they are blocked by a corticotropin-releasing factor antagonist and reproduced by intracerebroventricular administration of corticotropin-releasing factor. Moreover, mental stress-induced colonic motor alterations are mediated by the autonomic nervous system rather than by the hypothalamopituitary axis because they are not abolished by hypophysectomy.

Selective stimulation of colonic motor response to a meal by sigma ligands in dogs.

The influence of central vs. peripheral administration of sigma ligands (dl- and l-N-allylnormetazocine, 1-3-di-o-tolylguanidine, (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene and phencyclidine on colonic motility was investigated in fasted and fed dogs equipped with strain-guage transducers implanted on proximal and transverse colon. When injected intravenously at a dose of 0.25 mg/kg just before feeding, dl- or d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene (but not phencyclidine) enhanced the colonic motor response to a meal by increasing the 0-4-hour motility indexes from 64.1%-159.3% in both the proximal and transverse colon but had no effect on colonic motility in fasted animals or animals injected intracerebroventricularly. The motor-stimulatory effects of d-N-allylnormetazocine (1 mg/kg), 1-3-di-o-tolylguanidine (0.25 mg/kg), and (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene (1 mg/kg) were abolished after previous treatment with haloperidol (0.5 mg/kg, intravenous) but not after sulpiride (0.1 mg/kg) or (+) R-(+)-8-chloro-2,3,4,5-tetrahydro-3- methyl-5-phenyl-1-H-3-benzozepine-OH. Prazosin (0.1 mg/kg, intravenous) and 1-methyl-3-(2-indolyl)amino-5-phenyl-3H-1,4-benzodiazepin-2-one (0.01 mg/kg) also suppressed the enhancement of the colonic motor response to eating induced by d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+)cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene whereas naltrexone did not affect their effects. It is concluded that d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+)cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene stimulate the postprandial colonic motility in dogs by acting selectively on sigma receptors located peripherally and probably by affecting the release of cholecystokinin octapeptide through a central adrenergic mechanism.