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1.
Psychoneuroendocrinology ; 10(1): 103-8, 1985.
Article in English | MEDLINE | ID: mdl-2988003

ABSTRACT

Synaptic modulation refers to altered excitability of a synapse by a substance that does not produce a spike potential at the synapse. Available evidence points to the conclusion that beta-melanocyte stimulating hormone (beta-MSH) modulates synaptic transmission through monosynaptic pathways in the cat spinal cord. Earlier evidence is reviewed, and new data are presented. In the first experiments populations of cells contributing to a knee jerk were studied using the Lloyd preparation, and MSH was found to increase the monosynaptic reflex. With intracellular single unit recording techniques, beta-MSH was found to facilitate recovery from synaptic transmission. With extracellular single unit recording techniques and iontophoretic methods for drug application, beta-MSH has been found to increase the probability of generation of single spike potentials by alpha-motoneurons in response to orthodromic stimulation. Administration of beta-MSH did not cause spontaneous discharge of alpha-motoneurons. The physiological and pharmacological importance of synaptic modulation is discussed.


Subject(s)
Melanocyte-Stimulating Hormones/pharmacology , Spinal Cord/drug effects , Synaptic Transmission/drug effects , Animals , Anterior Horn Cells/drug effects , Cats , Decerebrate State , Reflex, Monosynaptic/drug effects , Synapses/drug effects
2.
Biomed Biochim Acta ; 44(5): 773-8, 1985.
Article in English | MEDLINE | ID: mdl-4062923

ABSTRACT

The opioid antagonist naloxone induced tonic contraction ("gut dependence") of isolated ilia of both morphine dependent WKY-rats and WKY-rats chronically stressed by immobilization. Morphine and met-enkephalin but neither dynorphine nor leu-enkephalin antagonized the naloxone induced "gut dependence" of isolated ilia obtained from morphine dependent WKY-rats. Met-enkephalin as well as dynorphine inhibited the "gut dependence" of chronically stressed rats; morphine and leu-enkephalin had no inhibitory effect. These differences between influences of different opioid peptides on "gut dependence" of morphine dependent rats versus "gut dependence" of rats chronically stressed by immobilization suggest that chronic stress induced or facilitated production of a different population of receptors.


Subject(s)
Endorphins/physiology , Ileum/physiopathology , Morphine Dependence/physiopathology , Stress, Physiological/physiopathology , Animals , Endorphins/pharmacology , Ileum/drug effects , Immobilization , In Vitro Techniques , Male , Muscle Contraction/drug effects , Naloxone/pharmacology , Rats , Rats, Inbred WKY
5.
Peptides ; 3(5): 851-7, 1982.
Article in English | MEDLINE | ID: mdl-6184702

ABSTRACT

Amino-terminal fragments of substance P (SP), SP(1-7) and SP(1-8), were found to produce naloxone-reversible antinociception in the mouse similar to that produced by SP. Similar to SP, these peptides produce antinociception only within a narrow dose range. They have no activity on smooth muscle or blood pressure. These results suggest that contrary to peripheral effects of SP, which are mediated by receptors which recognize the carboxy-terminal part of the SP molecule, certain central actions of SP are mediated by receptors which recognize the amino-terminal part of the SP molecule. SP may be metabolized to this active fragment prior to its action at these receptors.


Subject(s)
Peptide Fragments/pharmacology , Substance P/pharmacology , Analgesia , Animals , Brain/metabolism , Brain Chemistry , Fluorescent Antibody Technique , Kinetics , Pain/physiopathology , Radioimmunoassay , Rats , Receptors, Cell Surface/metabolism , Receptors, Neurokinin-1 , Synaptic Membranes/metabolism
6.
Ann N Y Acad Sci ; 398: 377-87, 1982.
Article in English | MEDLINE | ID: mdl-6961864

ABSTRACT

Endorphin levels were measured in 51 cerebrospinal fluid samples from 27 opioid-dependent or postdependent subjects. Radioreceptor assay showed the endorphin levels to be higher than those found in normal subjects. These high levels were found even while subjects were on methadone maintenance. The duration of opioid dependence was positively correlated with fraction I values. Both fractions tended to be lower during early withdrawal than late withdrawal. In naltrexone-maintained patients, radioreceptor assay showed FII to be greatly elevated, but electrophoresis and HPLC indicated that the elevations were not due to a peptide. Thus, the possibility of unextracted naltrexone metabolites remains at least a partial explanation for this apparent FII elevation.


Subject(s)
Endorphins/cerebrospinal fluid , Opioid-Related Disorders/cerebrospinal fluid , Adult , Humans , Male , Methadone/therapeutic use , Middle Aged , Naltrexone/therapeutic use , Opioid-Related Disorders/rehabilitation , Substance Withdrawal Syndrome/cerebrospinal fluid
7.
Brain Res ; 202(2): 365-72, 1980 Dec 08.
Article in English | MEDLINE | ID: mdl-6159948

ABSTRACT

Substance P (SP) applied by iontophoresis at different current strengths to single motoneurons of cat spinal cord did not cause these units to discharge. SP produced a gradual and prolonged change in synaptic excitability as measured by response to dorsal root stimulation. The effect outlasted application of SP. The lowest effective dose of SP diminished motoneuron response to dorsal root stimulation (inhibitory modulation). Doses 2-4 times as great enhanced the response to dorsal root stimulation (facilitatory modulation) without causing the motoneuron to discharge spontaneously. These observations suggest that one physiological role of SP is modulation of synaptic transmission, i.e. alteration of efficacy of transmission without acting as a primary transmitter at the postsynaptic membrane.


Subject(s)
Reflex, Monosynaptic/drug effects , Substance P/pharmacology , Animals , Cats , Evoked Potentials/drug effects , Motor Neurons/drug effects , Neural Inhibition/drug effects , Spinal Cord/drug effects , Synaptic Transmission/drug effects
10.
Fed Proc ; 38(9): 2344-7, 1979 Aug.
Article in English | MEDLINE | ID: mdl-456622

ABSTRACT

The phrase "synaptic modulation," to describe a role of neurotropic peptides, has been used in a number of different ways by a number of different investigators. Using the phrase in its original context, i.e. altered (increased or decreased) synaptic excitability without reference to site or mode of action, evidence is presented that substance P modulates synaptic transmission of cat alpha-motoneurons. The effect appears to be biphasic, with low doses inhibiting, and high doses facilitating synaptic transmission.


Subject(s)
Substance P/physiology , Melanocyte-Stimulating Hormones/physiology , Synapses/physiology
11.
Proc Natl Acad Sci U S A ; 75(9): 4573-6, 1978 Sep.
Article in English | MEDLINE | ID: mdl-279936

ABSTRACT

The peptide-Z-Pro-D-Leu, injected daily in mice receiving morphine chronically, was found to prevent development of physical dependence as measured by changes in body temperature and body weight due either to abrupt or to naloxone-induced withdrawal. On the other hand, administration of Z-Pro-D-Leu only on the last day of morphine treatment did not alter the overt signs of withdrawal. Daily administration of Z-Pro-D-Leu was also effective in blocking the development of tolerance to the analgesic and the hypothermic effects of subsequent challenge doses of morphine. However, the peptide treatment did not alter the acute effects of a challenge dose of morphine on either analgesia or body temperature. No effects on memory were noted, as evaluated in a one-trial passive avoidance task. Clinical implications of the use of Z-Pro-D-Leu are discussed.


Subject(s)
Dipeptides/pharmacology , Drug Tolerance , Morphine Dependence/prevention & control , Animals , Body Temperature Regulation/drug effects , Body Weight/drug effects , Humans , Male , Mice , Morphine/pharmacology , Naloxone/pharmacology , Pain/physiopathology , Retention, Psychology/drug effects
12.
Eur J Pharmacol ; 46(4): 315-22, 1977 Dec 15.
Article in English | MEDLINE | ID: mdl-590341

ABSTRACT

Actions of beta-MSH and of melatonin on the recovery cycle of single spinal neurones were studied in the decerebrate-spinal cat. beta-MSH facilitated the rate of post-excitation recovery of alpha-motoneurones and some internuncial neurones, and melatonin inhibited the rate of post-excitation recovery. These observations provide additional evidence that beta-MSH functions in the nervous system as a modulator, and may help explain actions of beta-MSH in modifying acquisition of conditioned avoidance responses as well as its interaction with drugs such as morphine.


Subject(s)
Melanocyte-Stimulating Hormones/pharmacology , Motor Neurons/drug effects , Spinal Cord/drug effects , Animals , Blood Pressure/drug effects , Cats , Decerebrate State/physiopathology , Electric Stimulation , Evoked Potentials/drug effects , Melatonin/pharmacology , Motor Neurons/physiology , Spinal Cord/cytology , Swine , Time Factors
13.
Arzneimittelforschung ; 27(3): 681-3, 1977.
Article in English | MEDLINE | ID: mdl-194605

ABSTRACT

The polypeptides ACTH and ATCH4-10 (OI 63) witha sequence of amino acids H-Met-Glu-His-Phe-Arg-Trp-Gly-OH, have similar stimulating effects on motor units in lower mammals. Their actions differ primarily in that ACTH4-10 is not corticotropic. Since the corticotropic action of ACTH frequently presents a problem during its clinical use in treatment of motor unit diseases, the action of ACTH4-10 was studied in two patients with muscular atrophy. Prior to administration of ACTH4-10, stimulation of M. oppenens pollicis through the median nerve evoked muscle action potentials in both patients which progressively declined in amplitude. This decline was not observed subsequent to the infuscion of ACTH4-10 (3, 6 and 15 mg). The effect lasted partially in excess of at least 2 h. It is suggested that ACTH4-10 produces this effect by direct action on a peripheral component of the motor unit and/or indirectly by an action on the central nervous system.


Subject(s)
Action Potentials/drug effects , Adrenocorticotropic Hormone/analogs & derivatives , Muscles/drug effects , Neuromuscular Diseases/physiopathology , Adolescent , Adrenocorticotropic Hormone/pharmacology , Adrenocorticotropic Hormone/therapeutic use , Adult , Female , Humans , Male , Muscles/physiology , Neuromuscular Diseases/drug therapy , Peptide Fragments/therapeutic use
17.
Eur J Pharmacol ; 33(1): 99-105, 1975 Aug.
Article in English | MEDLINE | ID: mdl-170120

ABSTRACT

Acute treatment of rats with morphine (10 mg/kg) resulted in a marked reduction of motor response to inescapable electric footshock (EFS). Nalorphine (2mg/kg) antagonized this action of morphine. Pretreatment with synthetic ACTH 1-24 (10 IU) 60 min prior to testing also inhibited this morphine-induced reduction, whereas other ACTH-like peptides, lacking corticotrophic activity, were ineffective. ACTH 1-24 had no effect on the response of adrenalectomized rats to EFS after morphine. In intact rats dexamethasone pretreatment 4 hr prior to testing also antagonized the action of morphine on EFS. Taken together these findings suggest that ACTH 1-24 interferes with the antinociceptive action of morphine and that the integrity of the adrenal is essential for demonstration of this antagonism.


Subject(s)
Behavior, Animal/drug effects , Electroshock , Morphine/antagonists & inhibitors , Peptides/pharmacology , Adrenal Glands/physiology , Adrenalectomy , Adrenocorticotropic Hormone/pharmacology , Animals , Cosyntropin/pharmacology , Dexamethasone/pharmacology , Female , Melanocyte-Stimulating Hormones/pharmacology , Morphine/pharmacology , Nalorphine/pharmacology , Rats , Rats, Inbred Strains
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