Anand-Srivastava M B, Franks D J
Life Sci. 1985 Sep 2;37(9):857-67. doi: 10.1016/0024-3205(85)90521-1.
An adenosine-sensitive adenylate cyclase has been characterized in cultured mesenteric artery smooth muscle cells. N-Ethylcarboxamide-adenosine (NECA), N-Methylcarboxamide-adenosine (MECA), L-N6-phenylisopropyladenosine (PIA) and 2-chloroadenosine (2-cl-Ado) all stimulated adenylate cyclase in a concentration dependent manner. NECA was the most potent analog (EC50, 1 microM), whereas PIA (EC50, 15 microM), 2-Cl-Ado (EC50, 15 microM) and MECA (EC50, 24 microM), were less potent and had efficacies relative to NECA of 0.61, 0.61 and 0.65, respectively. Adenosine showed a biphasic effect: stimulation at lower concentrations and inhibition at higher concentrations, whereas 2' deoxyadenosine only inhibited adenylate cyclase activity. The stimulatory effect of NECA on adenylate cyclase was dependent on metal ion concentration and was blocked by 3-isobutyl-l-methylxanthine (IBMX) and 8-phenyltheophylline (8-PT). Adenylate cyclase from these cultured cells was also stimulated by other agonists such as epinephrine, norepinephrine, prostaglandins, dopamine, NaF and forskolin. The stimulation of adenylate cyclase by isoproterenol, epinephrine and norepinephrine was blocked by propranolol but not by phentolamine. On the other hand, phentolamine, propranolol and flupentixol all inhibited dopamine-stimulated adenylate cyclase activity. In addition, the stimulation by an optimal concentration of PIA was additive or almost additive with maximal stimulation caused by catecholamines and prostaglandins. These data indicate the presence of adenosine (Stimulatory "Ra"), catecholamine and prostaglandin receptors in mesenteric artery smooth muscle cells and suggest that these agents may exert their physiological actions through their interaction with their respective receptors coupled to adenylate cyclase.
已在培养的肠系膜动脉平滑肌细胞中对一种腺苷敏感性腺苷酸环化酶进行了特性描述。N-乙基甲酰胺-腺苷（NECA）、N-甲基甲酰胺-腺苷（MECA）、L-N6-苯基异丙基腺苷（PIA）和2-氯腺苷（2-Cl-Ado）均以浓度依赖性方式刺激腺苷酸环化酶。NECA是最有效的类似物（半数有效浓度[EC50]，1微摩尔），而PIA（EC50，15微摩尔）、2-Cl-Ado（EC50，15微摩尔）和MECA（EC50，24微摩尔）效力较低，相对于NECA的效能分别为0.61、0.61和0.65。腺苷呈现双相效应：在较低浓度时刺激，在较高浓度时抑制，而2'-脱氧腺苷仅抑制腺苷酸环化酶活性。NECA对腺苷酸环化酶的刺激作用取决于金属离子浓度，并被3-异丁基-1-甲基黄嘌呤（IBMX）和8-苯基茶碱（8-PT）阻断。来自这些培养细胞的腺苷酸环化酶也受到其他激动剂的刺激，如肾上腺素、去甲肾上腺素、前列腺素、多巴胺、氟化钠和福斯高林。异丙肾上腺素、肾上腺素和去甲肾上腺素对腺苷酸环化酶的刺激作用被普萘洛尔阻断，但不被酚妥拉明阻断。另一方面，酚妥拉明、普萘洛尔和氟哌噻吨均抑制多巴胺刺激的腺苷酸环化酶活性。此外，最佳浓度的PIA引起的刺激与儿茶酚胺和前列腺素引起的最大刺激呈相加或几乎相加作用。这些数据表明肠系膜动脉平滑肌细胞中存在腺苷（刺激性“Ra”）、儿茶酚胺和前列腺素受体，并提示这些物质可能通过与各自与腺苷酸环化酶偶联的受体相互作用来发挥其生理作用。
