Martin T J, Sim L J, Selley D E, deMontis M G, Childers S R
Dept of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina, USA.
Synapse. 1997 Nov;27(3):177-82. doi: 10.1002/(SICI)1098-2396(199711)27:3<177::AID-SYN3>3.0.CO;2-A.
Intracerebroventricular administration of beta-funaltrexamine (beta-FNA) reduces the density of mu opioid receptors as measured by in situ autoradiography by 40-50% throughout the brain, with little regional variation [Martin et al. (1993) J. Pharmacol. Exp. Ther. 267:506-514] Recently an assay has been developed to study opioid stimulation of [35S]GTP-gamma-S binding autoradiographically in situ using slide-mounted brain sections [Sim et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92:7242-7246]. The present study was undertaken to determine the effect of mu opioid receptor alkylation on G protein activation by the mu opioid agonist DAMGO. Animals were injected intracerebroventricularly with 40 nmol of beta-FNA or saline and sacrificed 24 hours later. DAMGO stimulated [35S]GTP-gamma-S binding with an anatomical specificity consistent with the localization of mu opioid receptors. The percent stimulation by DAMGO ranged from approximately 50 to 100% in the regions studied. beta-FNA significantly decreased G protein activation by DAMGO in regions that are consistent with its reported long-lasting and insurmountable antagonism of the antinociceptive (medial thalamus, central gray) and reinforcing (nucleus accumbens) effects of mu opioid agonists [Adams et al. (1990) J. Pharmacol. Exp. Ther. 255:1027-1032; Martin et al. (1995) J. Pharmacol. Exp. Ther. 272:1135-1140]. However, the effects of beta-FNA were not equal in all brain regions. This may indicate regional differences in the coupling efficiency of mu opioid receptors with G proteins, or in the effects of beta-FNA on mu opioid receptor binding or on mu opioid receptor-stimulated G protein activity.
通过原位放射自显影法测量，脑室内注射β-芬基曲马胺（β-FNA）可使全脑μ阿片受体密度降低40%-50%，且区域差异很小[马丁等人（1993年）《药理学与实验治疗学杂志》267:506-514]。最近开发了一种检测方法，用于在载玻片上的脑切片上通过放射自显影原位研究阿片类药物对[35S]GTP-γ-S结合的刺激作用[西姆等人（1995年）《美国国家科学院院刊》92:7242-7246]。本研究旨在确定μ阿片受体烷基化对μ阿片激动剂DAMGO激活G蛋白的影响。给动物脑室内注射40 nmol的β-FNA或生理盐水，24小时后处死。DAMGO刺激[35S]GTP-γ-S结合，其解剖学特异性与μ阿片受体的定位一致。在所研究的区域中，DAMGO的刺激百分比范围约为50%至100%。β-FNA在与其报道的对μ阿片激动剂的镇痛（内侧丘脑、中央灰质）和强化（伏隔核）作用的持久且不可克服的拮抗作用一致的区域中，显著降低了DAMGO对G蛋白的激活作用[亚当斯等人（1990年）《药理学与实验治疗学杂志》255:1027-1032；马丁等人（1995年）《药理学与实验治疗学杂志》272:1135-1140]。然而，β-FNA在所有脑区的作用并不相同。这可能表明μ阿片受体与G蛋白的偶联效率存在区域差异，或者β-FNA对μ阿片受体结合或对μ阿片受体刺激的G蛋白活性的影响存在区域差异。
