The dynamic relationship between mu and kappa opioid receptors in body temperature regulation

被引:20
作者
Chen, XH [1 ]
McClatchy, DB [1 ]
Geller, EB [1 ]
Tallarida, RJ [1 ]
Adler, MW [1 ]
机构
[1] Temple Univ, Sch Med, Ctr Subst Abuse Res, Philadelphia, PA 19140 USA
关键词
Mu and kappa opioid receptors; body temperature; CTAP; nor-BNI; rat;
D O I
10.1016/j.lfs.2005.04.084
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Previous studies demonstrated that intracerebroventricular (icv) injection of a kappa opioid receptor agonist decreased, and a mu agonist increased, body temperature (T-b) 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 T-b. 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 T-b 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 T-b in unrestrained rats. CTAP significantly antagonized the T-b increase induced by icv injection of nor-BNI. Injection of 5 or 10 nmol of CTAP alone significantly decreased the T-b, 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 T-b. (c) 2005 Elsevier Inc. All rights reserved.
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页码:329 / 333
页数:5
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