Maher C E, Eisenach J C, Pan H L, Xiao R, Childers S R
Department of Physiology and Pharmacology, Center for the Neurobiological Investigation of Drug Abuse, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Brain Res. 2001 Mar 23;895(1-2):1-8. doi: 10.1016/s0006-8993(00)03093-6.
Previous studies have shown that chronic i.v. treatment with morphine or heroin decreased mu opioid receptor activation of G-proteins in specific brain regions. The present study examined the effect of intrathecal (i.t.) morphine administration on receptor/G-protein coupling in the spinal cord. In spinal cord membranes, [35S]GTP gamma S binding was stimulated by agonists of several G-protein-coupled receptors, including mu opioid (DAMGO), delta opioid (DPDPE), GABA(B) (baclofen), cannabinoid CB(1) (WIN 55,212-2), muscarinic cholinergic (carbachol) and adenosine A(1) (PIA). [35S]GTP gamma S autoradiography revealed that most of this agonist activation of G-proteins was localized to laminae I and II of dorsal horn. To determine the effects of chronic morphine on these receptor activities, rats were treated for 7 days with 0.11 mg/kg/day i.t. morphine, and receptor activation of G-proteins was determined by [35S]GTP gamma S autoradiography of brain and spinal cord. In spinal cord sections, chronic morphine treatment decreased DAMGO-stimulated [35S]GTP gamma S binding in laminae I and II at all levels of spinal cord examined. There were no effects of morphine treatment on [35S]GTP gamma S stimulation in spinal cord by other receptor systems examined (Adenosine A(1) and GABA(B)), and no significant effects of chronic i.t. morphine treatment were observed in brain sections. These data show that homologous desensitization of mu receptor/G-protein coupling occurs specifically in spinal cord following chronic morphine administration.
先前的研究表明，长期静脉注射吗啡或海洛因会降低特定脑区中G蛋白的μ阿片受体激活。本研究检测了鞘内注射吗啡对脊髓中受体/G蛋白偶联的影响。在脊髓膜中，几种G蛋白偶联受体的激动剂可刺激[35S]GTPγS结合，包括μ阿片（DAMGO）、δ阿片（DPDPE）、GABA(B)（巴氯芬）、大麻素CB(1)（WIN 55,212-2）、毒蕈碱胆碱能（卡巴胆碱）和腺苷A(1)（PIA）。[35S]GTPγS放射自显影显示，G蛋白的这种激动剂激活大部分定位于背角的I层和II层。为了确定慢性吗啡对这些受体活性的影响，大鼠接受0.11mg/kg/天的鞘内吗啡治疗7天，并通过脑和脊髓的[35S]GTPγS放射自显影测定G蛋白的受体激活。在脊髓切片中，慢性吗啡治疗降低了在所检测的脊髓各水平I层和II层中DAMGO刺激的[35S]GTPγS结合。吗啡治疗对所检测的其他受体系统（腺苷A(1)和GABA(B)）在脊髓中对[35S]GTPγS的刺激没有影响，并且在脑切片中未观察到慢性鞘内吗啡治疗的显著影响。这些数据表明，慢性吗啡给药后，μ受体/G蛋白偶联的同源脱敏特异性地发生在脊髓中。
