Ayajiki K, Okamura T, Toda N
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
J Pharmacol Exp Ther. 1994 Aug;270(2):795-801.
In cat middle cerebral arterial strips denuded of the endothelium, nicotine produced a relaxation that was abolished by treatment with hexamethonium. The relaxation was partially inhibited by treatment with NG-nitro-L-arginine (L-NNA), a nitric oxide (NO) synthase inhibitor, and oxyhemoglobin, an NO scavenger. The remaining relaxation in the media containing L-NNA was abolished in the strips made unresponsive to calcitonin gene-related peptide (CGRP) by its repeated application. However, this was not the case when the strips were made tachyphylaxic to vasoactive intestinal polypeptide. The nicotine-induced relaxation was also partially attenuated by pretreatment with capsaicin; the remaining relaxation was abolished by L-NNA but not by its D-enantiomer. The inhibitory effect of L-NNA was reversed by L- but not D-arginine. Histochemical study revealed that injections of ethanol into the vicinity of pterygopalatine ganglion abolished the positive staining for nicotinamide adenine dinucleotide phosphate diaphorase activity and the CGRP immunoreactivity in perivascular nerves innervating the middle cerebral artery of the ipsilateral side. The nicotine-induced relaxation in the middle cerebral artery from the ethanol-injected side was markedly inhibited compared with that from the nontreated side, whereas the relaxations induced by exogenously applied NO and CGRP were unaffected. We conclude that nicotine stimulates nicotinic receptors in nerve terminals and liberates NO or NO-like substance(s) and CGRP as neurotransmitters in cat middle cerebral arteries.
在去除内皮的猫大脑中动脉条中，尼古丁可产生舒张作用，六甲铵处理可消除该作用。用一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸（L-NNA）和NO清除剂氧合血红蛋白处理可部分抑制该舒张作用。在含有L-NNA的培养基中，通过反复应用降钙素基因相关肽（CGRP）使条带对其无反应后，剩余的舒张作用消失。然而，当条带对血管活性肠肽产生快速耐受性时，情况并非如此。辣椒素预处理也可部分减弱尼古丁诱导的舒张作用；剩余的舒张作用可被L-NNA消除，但不能被其D-对映体消除。L-NNA的抑制作用可被L-精氨酸而非D-精氨酸逆转。组织化学研究显示，向翼腭神经节附近注射乙醇可消除同侧大脑中动脉周围神经中烟酰胺腺嘌呤二核苷酸磷酸黄递酶活性的阳性染色和CGRP免疫反应性。与未处理侧相比，注射乙醇侧大脑中动脉中尼古丁诱导的舒张作用明显受到抑制，而外源性应用NO和CGRP诱导的舒张作用不受影响。我们得出结论，尼古丁刺激神经末梢中的烟碱受体，释放NO或NO样物质以及CGRP作为猫大脑中动脉中的神经递质。
