Mulder A H, Wardeh G, Kazmierski W, Hruby V J
Department of Pharmacology, Free University Medical Faculty, Amsterdam, The Netherlands.
Eur J Pharmacol. 1988 Nov 15;157(1):109-14. doi: 10.1016/0014-2999(88)90477-3.
In the present study the opioid receptor antagonist properties of the conformationally constrained cyclic octapeptide D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP), which is derived from somatostatin, were investigated, using in vitro functional paradigms of central mu-, delta- and kappa-opioid receptors. Activation of mu-opioid receptors by the enkephalin analogues DADLE or DAGO resulted in a strong inhibition (by 60-70%) of the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices. This inhibitory effect was antagonized by CTP in a competitive fashion (pA2 value 7.7-7.9). Activation of kappa-opioid receptors by bremazocine selectively inhibited (by 45-50%) the release of [3H]dopamine (DA) from striatal slices, whereas activation of delta-opioid receptors by DADLE caused an inhibition (by 55-60%) of striatal [14C]acetylcholine (ACh) release, but neither of these inhibitory effects was affected by CTP. By itself, CTP inhibited cortical [3H]NA release (by 35-40%), but it did not affect the release of [3H]DA nor that of [14C]ACh from striatal slices. The inhibitory effect of CTP was not antagonized by naloxone. The data indicate that CTP selectively antagonizes mu-opioid receptors, involved in presynaptic inhibition of NA release in the brain. In addition, the peptide by itself causes an inhibition of NA release via a non-opioid receptor-mediated process.
在本研究中，使用中枢μ-、δ-和κ-阿片受体的体外功能范式，研究了源自生长抑素的构象受限环八肽D-苯丙氨酸-半胱氨酸-酪氨酸-D-色氨酸-赖氨酸-苏氨酸-青霉胺-苏氨酸-NH2（CTP）的阿片受体拮抗剂特性。脑啡肽类似物DADLE或DAGO激活μ-阿片受体会导致[3H]去甲肾上腺素（NA）从灌流皮层切片中（电诱发）释放受到强烈抑制（60%-70%）。CTP以竞争性方式拮抗这种抑制作用（pA2值为7.7-7.9）。布马佐辛激活κ-阿片受体选择性抑制（45%-50%）纹状体切片中[3H]多巴胺（DA）的释放，而DADLE激活δ-阿片受体导致纹状体[14C]乙酰胆碱（ACh）释放受到抑制（55%-60%），但这些抑制作用均不受CTP影响。CTP本身可抑制皮层[3H]NA释放（35%-40%），但不影响纹状体切片中[3H]DA或[14C]ACh的释放。CTP的抑制作用不受纳洛酮拮抗。数据表明，CTP选择性拮抗参与大脑中NA释放突触前抑制的μ-阿片受体。此外，该肽本身通过非阿片受体介导的过程导致NA释放受到抑制。
