Interaction of cholecystokinin and somatostatin with a selective mu-opioid agonist and mu- and kappa-antagonists in thermoregulation.
We examined the effects of intracerebroventricular (i.c.v.) injections of cholecystokinin-octapeptide (CCK-8) and somatostatin (SST) and the interactions of these neuropeptides with the selective opioid antagonists, CTAP (mu) and nor-BNI (kappa) and the mu-agonist, PL017, on body temperature (Tb) of the rat at normal ambient temperature (21 +/- 0.5 degrees C). CCK-8 produced short-lasting (15-60 min), dose-related increases in Tb in a dose range of 20 to 900 ng but did not change the Tb at lower doses (0.1-2 ng). Lower doses of SST (1 and 2 micrograms) produced hyperthermia (30-60 min) and a higher dose of SST (10 micrograms) caused hypothermia (30-45 min). PL017 (1 microgram, i.c.v.), alone and in combination with CCK-8, produced hyperthermia. The CCK-8 (300 ng)-induced hyperthermia was blocked by pretreatment of rats with CTAP (1 microgram, i.c.v.), suggesting that the higher doses of CCK-8 increase Tb through the interaction with mu-receptors or the enhancement of release of endogenous opioids acting on the mu-receptor. The hyperthermia elicited by a lower dose of SST (1 microgram) was prevented by pretreatment with CTAP but not with nor-BNI (1 microgram, i.c.v.). Pretreatment with nor-BNI blocked the higher dose (10 micrograms) of SST-induced hypothermia. PL017 or CTAP did not prevent the hypothermic effect of that dose of SST. These results indicate that a lower dose of SST (1 microgram) stimulates the mu-receptor (directly or indirectly) and a higher dose (10 micrograms) interacts with the kappa-receptor in regulation of Tb. Thus, the effects of both CCK-8 and SST on Tb appear to involve the endogenous opioid system.
Ghosh
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S
Department of Pharmacology, Temple University, School of Medicine, Philadelphia, PA 19104, USA.
Geller
E B
EB
Adler
M W
MW
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
C529311:CTAP octapeptide; D004723:Endorphins; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; C044708:morphiceptin, N-Me-Phe(3)-; D002766:Cholecystokinin