Rat central ORL-1 receptor uncouples from adenylyl cyclase during membrane preparation

被引:17
作者
Okawa, H
Hirst, RA
Smart, D
McKnight, AT
Lambert, DG [1 ]
机构
[1] Univ Leicester, Leicester Royal Infirm, Dept Anaesthesia, Leicester LE1 5WW, Leics, England
[2] Parke Davis Neurosci Res Ctr, Cambridge CB2 2QB, England
关键词
orphan opioid receptor; nociceptin; cannabinoids; rat brain; cyclic adenosine monophosphate;
D O I
10.1016/S0304-3940(98)00228-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nociceptin/orphanin FQ is the endogenous agonist of the orphan receptor ORL-1. In this study, we sought to examine any possible regional differences of nociceptin binding using [I-125]Tyr(14)-nociceptin, and of agonist induced inhibition of CAMP formation in membranes prepared from cerebrocortex, cerebellum and brainstem. The binding of [I-125]Tyr(14)-nociceptin was concentration-dependent and saturable, with B-max and pK(d) (pM) values of 179.7 +/- 15.3 fmol/mg protein and 10.26 +/- 0.09 (60.0), 12.4 +/- 1.8 fmol/mg protein and 10.44 +/- 0.07 (37.0), 52.3 +/- 0.8 fmol/mg protein and 10.16 +/- 0.08 (74.0) in cerebrocortical, cerebella and brainstem membranes, respectively. In all preparations, nociceptin up to 1 mu M failed to inhibit basal and forskolin stimulated CAMP formation. In all tissues forskolin stimulated and nabilone (acting at the central cannabinoid receptor) inhibited CAMP formation. Collectively these data report regional differences in ORL-1 receptor expression and that these receptors uncouple during membrane preparation. (C) 1998 Elsevier Science Ireland Ltd.
引用
收藏
页码:49 / 52
页数:4
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