Ahn H S, Mishra R K, Demirjian C, Makman M H
Brain Res. 1976 Nov 12;116(3):437-54. doi: 10.1016/0006-8993(76)90492-3.
Adenylate cyclase activity (AC) of homogenates of monkey frontal cortex was stimulated by catecholamines (dopamine, norepinephrine and isoproterenol), apomorphine, clonidine, NaF and GPP(NH)P. The increment in activity due to dopamine was enhanced in the presence of GPP(NH)P. The AC was also stimulated by 0.2-0.4 mM Ca2+ in the presence of 0.2 mM EGTA; at 0.8 mM Ca2+ had little or no influence on basal or NaF-stimulated activity. However, as Ca2+ concentration was increased from 0.2 to 0.8 mM stimulation by dopamine or GPP(NH)P was progressively inhibited. These results suggest a possible function of Ca2+ in modulating neurotransmitter stimulation of AC in the monkey frontal cortex. The AC exhibited higher sensitivity to dopamine than to norepinephrine or isoproterenol; however dopamine and norepinephrine caused the same maximum stimulation of the enzyme, a stimulation womewhat greater than that produced by isoproterenol. An additivity in stimulating AC was observed for dopamine and isoproterenol but not for dopamine and norepinephrine. Norepinephrine- or dopamine-stimulated AC was effectively blocked by fluphenazine and other dopamine-receptor blocking agents (relative potency for blockade; fluphenazine, haloperidol greater than clozapine, thioridazine greater than pimozide) but not by propranolol, a beta-receptor blocker. In contrast, isoproterenol-stimulated AC was antagonized by propranolol or alprenolol but not by fluphenazine. On the basis of these results, at least two distinct receptors appear to be associated with AC of monkey frontal cortex: (1) a beta-receptor stimulated by isoproterenol and (2) a new type of dopamine or dopamine-norepinephrine receptor, stimulated by either dopamine or norepinephrine. This latter system differs from more typical dopamine receptors found in caudate, retina and limbic cortex in that (a) it is not stimulated by 1-(3,4-dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine (S584); (b) it is stimulated significantly by the putative alpha-receptor agonist, clonidine; (c) it is more sensitive to blockade by clozapine than primate retina or caudate; also the sensitivity to haloperidol is greater than has been reported for non-primate caudate; (d) it is very sensitive to stimulation by norepinephrine and to blockade by phentolamine (an alpha-receptor blocker).
猴额叶皮质匀浆的腺苷酸环化酶活性（AC）受到儿茶酚胺（多巴胺、去甲肾上腺素和异丙肾上腺素）、阿扑吗啡、可乐定、氟化钠和GPP(NH)P的刺激。在GPP(NH)P存在的情况下，多巴胺引起的活性增加增强。在0.2 mM乙二醇双（2-氨基乙基醚）四乙酸（EGTA）存在时，AC也受到0.2 - 0.4 mM钙离子（Ca2+）的刺激；在0.8 mM Ca2+时，对基础或氟化钠刺激的活性几乎没有影响。然而，随着Ca2+浓度从0.2 mM增加到0.8 mM，多巴胺或GPP(NH)P的刺激作用逐渐受到抑制。这些结果表明Ca2+在调节猴额叶皮质中神经递质对AC的刺激方面可能具有作用。AC对多巴胺的敏感性高于去甲肾上腺素或异丙肾上腺素；然而，多巴胺和去甲肾上腺素对该酶的最大刺激作用相同，这种刺激作用略大于异丙肾上腺素产生的刺激作用。观察到多巴胺和异丙肾上腺素对AC的刺激具有相加性，但多巴胺和去甲肾上腺素则没有。氟奋乃静和其他多巴胺受体阻断剂（阻断的相对效力；氟奋乃静、氟哌啶醇大于氯氮平、硫利达嗪大于匹莫齐特）可有效阻断去甲肾上腺素或多巴胺刺激的AC，但β受体阻断剂普萘洛尔则不能。相反，异丙肾上腺素刺激的AC可被普萘洛尔或阿普洛尔拮抗，但不能被氟奋乃静拮抗。基于这些结果，至少有两种不同的受体似乎与猴额叶皮质的AC相关：（1）一种由异丙肾上腺素刺激的β受体；（2）一种新型的多巴胺或多巴胺 - 去甲肾上腺素受体，可被多巴胺或去甲肾上腺素刺激。后一种系统与尾状核、视网膜和边缘皮质中发现的更典型的多巴胺受体不同，在于：（a）它不受1-(3,4 - 二羟基苄基)-4-(2 - 嘧啶基)哌嗪（S584）刺激；（b）它受到假定的α受体激动剂可乐定的显著刺激；（c）它对氯氮平阻断的敏感性高于灵长类动物视网膜或尾状核；对氟哌啶醇的敏感性也高于非灵长类动物尾状核的报道；（d）它对去甲肾上腺素的刺激和酚妥拉明（一种α受体阻断剂）的阻断非常敏感。
