The dynamic relationship between mu and kappa opioid receptors in body temperature regulation.
Previous studies demonstrated that intracerebroventricular (icv) injection of a kappa opioid receptor agonist decreased, and a mu agonist increased, body temperature (Tb) in rats. A dose-response study with the selective kappa antagonist nor-binaltorphimine (nor-BNI) showed that a low dose (1.25 nmol, icv) alone had no effect, although a high dose (25 nmol, icv) increased Tb. It was hypothesized that the hyperthermia induced by nor-BNI was the result of the antagonist blocking the kappa opioid receptor and releasing its inhibition of mu opioid receptor activity. To determine whether the Tb increase caused by nor-BNI was a mu receptor-mediated effect, we administered the selective mu antagonist CTAP (1.25 nmol, icv) 15 min after nor-BNI (25 nmol, icv) and measured rectal Tb in unrestrained rats. CTAP significantly antagonized the Tb increase induced by icv injection of nor-BNI. Injection of 5 or 10 nmol of CTAP alone significantly decreased the Tb, and 1.25 nmol of nor-BNI blocked that effect, indicating that the CTAP-induced hypothermia was kappa-mediated. The findings strongly suggest that mu antagonists, in blocking the basal hyperthermia mediated by mu receptors, can unmask the endogenous kappa receptor-mediated hypothermia, and that there is a tonic balance between mu and kappa opioid receptors that serves as a homeostatic mechanism for maintaining Tb.
Chen
Xiaohong
X
Center for Substance Abuse Research, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA. chenyang@temple.edu
McClatchy
Daniel B
DB
Geller
Ellen B
EB
Tallarida
Ronald J
RJ
Adler
Martin W
MW
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004399:Dynorphins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin
C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010455:Peptides; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; D004399:Dynorphins