Izenwasser S, Búzás B, Cox B M
Department of Pharmacology, Uniformed Services University, Bethesda, Maryland.
J Pharmacol Exp Ther. 1993 Oct;267(1):145-52.
The regulation of adenylyl cyclase by opioid receptor types was characterized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putamen, a region not implicated in drug reinforcement. Both mu and delta opioid ligands inhibited adenylyl cyclase activity in the nucleus accumbens and in the caudate putamen of rat, whereas the kappa agonist, U69,593 (5 alpha, 7 alpha, 8 alpha)-(+)-N-methyl-N-[7-(pyrrolidinyl)-1-oxaspiro [4,5]dec-8-yl]-benzeneacetamide, was ineffective. The mu agonists, DAMGO and Tyr-D-Arg-Phe-Sar, were more potent inhibitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]-deltorphin II more potently inhibited adenylyl cyclase in nucleus accumbens than in caudate putamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg-Phe-Sar was antagonized by the mu-selective competitive antagonist, CTOP D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, beta-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase activity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]-deltorphin II was unaffected by these antagonists. Conversely, the delta-selective antagonists, ICI 174,864 N-allyl2-Tyr-(alpha-aminisobutyric acid)2-Phe-Leu-OH and naltrindole, blocked the effects of the delta but not the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbens and in caudate putamen is subject to regulation by both mu and delta opioid receptors.
阿片受体类型对腺苷酸环化酶的调节作用在大鼠伏隔核（一个与滥用药物的强化作用有关的脑区）和尾状壳核（一个与药物强化作用无关的区域）中得到了表征。μ和δ阿片配体均抑制大鼠伏隔核和尾状壳核中的腺苷酸环化酶活性，而κ激动剂U69,593（5α，7α，8α）-（+）-N-甲基-N-[7-（吡咯烷基）-1-氧杂螺[4,5]癸-8-基]-苯乙酰胺则无效。μ激动剂DAMGO和Tyr-D-Arg-Phe-Sar在尾状壳核中比在伏隔核中对该酶的抑制作用更强。δ选择性激动剂DSLET和[D-Ala2]-强啡肽II在伏隔核中比在尾状壳核中更有效地抑制腺苷酸环化酶。DAMGO和Tyr-D-Arg-Phe-Sar对该酶的抑制作用被μ选择性竞争性拮抗剂CTOP（D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2）以及非竞争性μ拮抗剂β-氟奈曲胺和纳洛嗪拮抗。δ选择性配体DPDPE、DSLET和[D-Ala2]-强啡肽II对腺苷酸环化酶活性的抑制作用不受这些拮抗剂的影响。相反，δ选择性拮抗剂ICI 174,864（N-烯丙基2-Tyr-（α-氨基异丁酸）2-Phe-Leu-OH）和纳曲吲哚可阻断δ阿片配体的作用，但不影响μ阿片配体的作用。伏隔核和尾状壳核中的腺苷酸环化酶活性受到μ和δ阿片受体的调节。
