published_or_final_version / Physiology / Master / Master of Philosophy

Thesis (Ph. D.)--University of Hawaii at Manoa, 1994. / Includes bibliographical references (leaves 85-101). / Microfiche. / xvi, 101 leaves, bound ill. 29 cm

No description available.

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.

David Chi-cheong Wan. / Bibliography: leaves 75-85 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1984

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1990. / Vita. Abstract. Includes bibliographies. Also available via the Internet.

Six studies were conducted to examine the role of endogenous opioid peptides in the regulation of ingestive behavior in the domestic fowl. In the first study, the dose-response relationships of two opioid antagonists, naloxone and naltrexone, were evaluated in Rock-Comish (RC) and Single-Comb White Leghorn (SCWL) cockerels. Naloxone and naltrexone decreased food and water intake in both stocks. In a separate experiment, the effect of naloxone on water intake was evaluated independent of food intake. Naloxone depressed water intake in normally hydrated and saline-loaded chicks. These results indicate endogenous opioid peptides influence food and water consumption independently in the domestic fowl. The sensitivities of RC and SCWL stocks to naloxone were compared in a second investigation. There was no difference in the efficacy of naloxone in attenuating ingestive behavior when the stocks were compared at either the same age or similar body weight. Therefore, genetic selection for meat or egg production has not significantly altered naloxone-sensitive opioid mechanisms regulating food and water intake in the domestic fowl. A third study extended the investigation of opioid regulation of ingestive behavior to Japanese quail (Coturnix coturnix japonica). Administration of naloxone attenuated feeding, but not drinking, suggesting that water in Japanese quail is not influenced by endogenous opioids. The fourth study was performed to determine whether opioid regulation of ingestive behavior in the domestic fowl is mediated at sites within the central nervous system or peripheral tissues. An initial experiment examined the effects of two opioid antagonists with differing ability to traverse the blood-brain barrier (bbb). Food and water intake were attenuated by both antagonists. However, at equally potent doses the antagonist which does not readily traverse the bbb (quaternary naloxone) was more effective than its congener which crosses the bbb (tertiary naloxone). Central administration of tertiary naloxone attenuated water consumption, but not feeding. No alterations in ingestive behavior were observed when these levels of tertiary naloxone were injected im. Therefore, these results suggest that opioid regulation of food intake occurs at sites outside the bbb, whereas water intake is at least, in part, centrally mediated. The remaining studies were conducted to identify the specific opioid receptor subtypes which mediate ingestive behavior in the domestic fowl. In the fifth study, ingestive responses to central (intracerebroventricular; ICV) and peripheral (im) administration of the mu agonist, morphiceptin, and the delta agonist, [Met⁵]·enkephalin, were studied. The mu and delta-opioid receptors are the receptors for which naloxone has the highest and lowest affinity, respectively. ICV administration of morphiceptin stimulated drinking, whereas im administration stimulated feeding. [Met⁵]·enkephalin stimulated food intake by both routes of administration. These results indicate that the mu opioid receptor mediates water intake in the central nervous system and food intake peripherally, while the delta-opioid receptor mediates food intake centrally and peripherally. Failure to detect central opioid mediation of food intake in previous studies was likely due to the low-affinity naloxone exhibits for the delta receptor. The final study examined the feeding, drinking, and temperature responses to ICV administration of ß-endorphin. ß-endorphin has equal affinity for the mu, delta, and epsilon opioid receptors. ICV administration of ß·endorphin induced increases in feeding, drinking, and colonic temperature in RC and SCWL. These studies indicate that endogenous opioid peptides influence food and water intake in the domestic fowl. Opioids appear to influence food and water consumption at sites within and outside the bbb, and via different receptor subtypes. Furthermore, there seems to be no difference in naloxone·sensitive opioid systems influencing ingestive behavior in meat and egg stocks of chickens. / Ph. D. / incomplete_metadata

Graduation date: 1999

published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Physiology / Master / Master of Philosophy