Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius
Pharmacological characterization of inhibitory effects of postsynaptic opioid and cannabinoid receptors on calcium currents in neonatal rat nucleus tractus solitarius
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DOI：
10.1038/sj.bjp.0706623
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发表时间：
2006-02-01
影响因子：
7.3
通讯作者：
Endoh, T
中科院分区：
文献类型：
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作者：
Endoh, T
利用膜片钳技术的全细胞结构研究了孤束核（NTS）神经元中阿片和大麻素受体的分布阿片受体、ORL受体和大麻素受体的选择性激动剂和拮抗剂实验表明，mu-阿片受体、kappa-阿片受体、ORL-1受体和CB1受体对ntc的VDCCs有抑制作用，而δ -阿片受体没有抑制作用。3 [D-Ala(2)、N-Me-Phe(4)、Gly(5)-ol]-脑啡肽（DAMGO； mu-阿片受体激动剂）、Orphanin FQ （ORL-1受体激动剂）和win55122 （CB1受体激动剂）对I-Ba的抑制呈浓度依赖性，IC50值分别为390 nM、220 nM和2.2 μ MG(i)-蛋白抗体的细胞内透析可减弱DAMGO-、Orphanin FQ-和win55,122诱导的i - ba .5抑制腺苷酸环化酶抑制剂预处理和蛋白激酶A （PKA）抑制剂的细胞内透析均能减弱win55122诱导的I-Ba抑制，但不能减弱DAMGO-和Orphanin FQ-诱导的抑制DAMGO和Orphanin FQ主要抑制N-和P/ q型vdcc，而WIN55,122.7抑制l型vdcc。这些结果表明，mu-和kappa-阿片受体和ORL-1受体通过G α (i)-蛋白β - γ亚基抑制N-和P/ q型vdcc，而CB1受体通过NTS中涉及PKA的G α (i)-蛋白抑制l型vdcc。
1 The profile of opioid and cannabinoid receptors in neurons of the nucleus tractus solitarius (NTS) has been studied using the whole-cell configuration of the patch clamp technique.2 Experiments with selective agonists and antagonists of opioid, ORL and cannabinoid receptors indicated that mu-opioid, kappa-opioid, ORL-1 and CB1, but not delta-opioid, receptors inhibit VDCCs in NTS.3 Application of [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]- enkephalin (DAMGO; mu-opioid receptor agonist), Orphanin FQ (ORL-1 receptor agonist) and WIN55,122 (CB1 receptor agonist) caused inhibition of I-Ba in a concentration-dependent manner, with IC50' s of 390 nM, 220 nM and 2.2 mu M, respectively.4 Intracellular dialysis of the G(i)-protein antibody attenuated DAMGO-,Orphanin FQ- and WIN55,122-induced inhibition of I-Ba.5 Both pretreatment with adenylate cyclase inhibitor and intracellular dialysis of the protein kinase A (PKA) inhibitor attenuated WIN55,122-induced inhibition of I-Ba but not DAMGO- and Orphanin FQ- induced inhibition.6 Mainly N- and P/Q-type VDCCs were inhibited by both DAMGO and Orphanin FQ, while L-type VDCCs were inhibited by WIN55,122.7 These results suggest that mu- and kappa-opioid receptors and ORL-1 receptor inhibit N- and P/Q-type VDCCs via G alpha(i)-protein beta gamma subunits, whereas CB1 receptors inhibit L-type VDCCs via G alpha(i)-proteins involving PKA in NTS.