CENTRAL NERVOUS SYSTEM REGULATION OF INTESTINAL MOTILITY: ROLE OF ENDOGENOUS OPIOID PEPTIDES (ENDORPHINS, ENKEPHALINS).

Persistent Link:
http://hdl.handle.net/10150/187571
Title:
CENTRAL NERVOUS SYSTEM REGULATION OF INTESTINAL MOTILITY: ROLE OF ENDOGENOUS OPIOID PEPTIDES (ENDORPHINS, ENKEPHALINS).
Author:
GALLIGAN, JAMES JOSEPH.
Issue Date:
1983
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The complex interaction between the central nervous system, the enteric nervous system and local and endocrine hormones enables drugs affecting gastrointestinal motility to produce their effects through multiple sites and mechanisms of action. Opiates are one class of drugs which can have dramatic effects on gastrointestinal function and the mechanisms for these actions have been the subject of intense study in recent years. These changes in motility have assumed increased importance following the discovery of several endogenous opioid peptides. In the present studies, centrally-administered morphine was more potent than peripherally-administered morphine at inhibiting intestinal propulsion and gastric emptying in rats. Direct measurement of intestinal motility revealed that the antipropulsive effects of morphine were due to an inhibition of intestinal contractions. The opioid peptide, β-endorphin, and a stabilized enkephalin analog, [D-Ala², Met⁵] enkephalinamide, also inhibited intestinal propulsion only after central administration. These effects were not blocked by a peripherally selective opioid receptor antagonist, diallylnormorphinium. These data indicated that there is an opioid sensitive mechanism in the brain of rats that, when activated, can inhibit intestinal motility. Physiological activation, by electroconvulsive shock or inescapable footshock, or pharamcological activation by kyotorphin (Tyr-Arg) treatment, did not affect gastrointestinal motility but did produce naloxone-reversible analgesia. These data indicate that the opioid mechanisms mediating analgesia and inhibition of intestinal motility are independent and may be a function of different receptor systems. Several opioid receptor selective agonists were used to determine the specific receptors mediating the analgesic and motility effects of centrally-administered opioids. Mu selective agonists produced analgesia and inhibition of intestinal transit, while delta receptor agonists produced analgesia only. Kappa agonists did not produce analgesia or an inhibition of intestinal motility. Mu receptors mediate the analgesic and intestinal motility effects of exogenously administered opioids, while delta receptors can mediate analgesia without altering gut motility. It appears then, that electroconvulsive shock, inescapable footshock and kyotorphin may produce their analgesic effects by releasing enkephalins, which are delta selective agonists. This accounts for the failure of these treatments to alter gastrointestinal motility while still producing the analgesic effects reported here.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Endorphins -- Physiological effect.; Gastrointestinal system -- Motility.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleCENTRAL NERVOUS SYSTEM REGULATION OF INTESTINAL MOTILITY: ROLE OF ENDOGENOUS OPIOID PEPTIDES (ENDORPHINS, ENKEPHALINS).en_US
dc.creatorGALLIGAN, JAMES JOSEPH.en_US
dc.contributor.authorGALLIGAN, JAMES JOSEPH.en_US
dc.date.issued1983en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe complex interaction between the central nervous system, the enteric nervous system and local and endocrine hormones enables drugs affecting gastrointestinal motility to produce their effects through multiple sites and mechanisms of action. Opiates are one class of drugs which can have dramatic effects on gastrointestinal function and the mechanisms for these actions have been the subject of intense study in recent years. These changes in motility have assumed increased importance following the discovery of several endogenous opioid peptides. In the present studies, centrally-administered morphine was more potent than peripherally-administered morphine at inhibiting intestinal propulsion and gastric emptying in rats. Direct measurement of intestinal motility revealed that the antipropulsive effects of morphine were due to an inhibition of intestinal contractions. The opioid peptide, β-endorphin, and a stabilized enkephalin analog, [D-Ala², Met⁵] enkephalinamide, also inhibited intestinal propulsion only after central administration. These effects were not blocked by a peripherally selective opioid receptor antagonist, diallylnormorphinium. These data indicated that there is an opioid sensitive mechanism in the brain of rats that, when activated, can inhibit intestinal motility. Physiological activation, by electroconvulsive shock or inescapable footshock, or pharamcological activation by kyotorphin (Tyr-Arg) treatment, did not affect gastrointestinal motility but did produce naloxone-reversible analgesia. These data indicate that the opioid mechanisms mediating analgesia and inhibition of intestinal motility are independent and may be a function of different receptor systems. Several opioid receptor selective agonists were used to determine the specific receptors mediating the analgesic and motility effects of centrally-administered opioids. Mu selective agonists produced analgesia and inhibition of intestinal transit, while delta receptor agonists produced analgesia only. Kappa agonists did not produce analgesia or an inhibition of intestinal motility. Mu receptors mediate the analgesic and intestinal motility effects of exogenously administered opioids, while delta receptors can mediate analgesia without altering gut motility. It appears then, that electroconvulsive shock, inescapable footshock and kyotorphin may produce their analgesic effects by releasing enkephalins, which are delta selective agonists. This accounts for the failure of these treatments to alter gastrointestinal motility while still producing the analgesic effects reported here.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectEndorphins -- Physiological effect.en_US
dc.subjectGastrointestinal system -- Motility.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.identifier.proquest8403228en_US
dc.identifier.oclc690258961en_US
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