Ishikawa S, Sperelakis N
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0576.
J Cardiovasc Pharmacol. 1989 Jun;13(6):836-45. doi: 10.1097/00005344-198906000-00005.
The possible involvement of three different second-messenger systems, namely cyclic AMP/protein kinase (PK)-A, cyclic GMP/PK-G, and diacylglycerol (DG)/PK-C systems, in the perivascular nerve terminals of guinea pig mesenteric artery was examined by intracellular microelectrode recording. Excitatory junction potentials (EJPs) were evoked by perivascular nerve stimulation. Isoproterenol (0.1 microM) enhanced the EJP amplitude without modifying the passive membrane properties of the vascular smooth muscle (VSM) cells. The facilitatory effect of isoproterenol on EJP amplitude was completely abolished by beta-adrenergic blockade (0.3 microM propranolol). Forskolin (activator of adenylate cyclase) also augmented the EJP amplitude in a concentration-dependent manner (EC50 congruent to 10 microM), without affecting the passive membrane properties of the VSM cells. In addition, forskolin (1-10 mM) markedly potentiated the isoproterenol-induced stimulation of EJP amplitude (EC50 congruent to 2 microM). A permeant analogue of cyclic AMP, 8-bromo-cyclic AMP (0.1 and 1 mM), enhanced the EJP amplitude, thus mimicking the effects of isoproterenol and forskolin. 8-Bromo-cyclic AMP had no effect on the resting potential or current-voltage relationship of the VSM cells, thus suggesting that the membrane properties of the VSM cells were not altered. 8-Bromo-cyclic GMP (1 mM) also augmented the EJP amplitude, but its facilitatory effect was weaker than that of 8-bromo-cyclic AMP. 8-Bromo-cyclic GMP hyperpolarized the VSM membrane by 4 mV and decreased the input resistance, presumably due to an increase in K+ conductance. Phorbol-12-myristate-13-acetate (PMA, 30-300 nM), a direct activator of PK-C, significantly enhanced the EJP amplitude after 40 min in a concentration-dependent manner, without affecting the resting potential of the VSM cells. From these results, we suggest that cyclic AMP/PK-A, cyclic GMP/PK-G, and DG/PK-C systems might be involved in regulation of the release of neurotransmitter in the perivascular nerve terminals. However, the possibility of some action on the postsynaptic VSM cell cannot be excluded.
采用细胞内微电极记录法，研究了豚鼠肠系膜动脉血管周围神经末梢中三种不同的第二信使系统，即环磷酸腺苷/蛋白激酶（PK）-A、环磷酸鸟苷/PK-G和二酰基甘油（DG）/PK-C系统的可能参与情况。血管周围神经刺激可诱发兴奋性接头电位（EJP）。异丙肾上腺素（0.1微摩尔）增强了EJP幅度，而未改变血管平滑肌（VSM）细胞的被动膜特性。β-肾上腺素能阻断剂（0.3微摩尔普萘洛尔）可完全消除异丙肾上腺素对EJP幅度的促进作用。福斯可林（腺苷酸环化酶激活剂）也以浓度依赖的方式增加了EJP幅度（半数有效浓度约为10微摩尔），且不影响VSM细胞的被动膜特性。此外，福斯可林（1-10毫摩尔）显著增强了异丙肾上腺素诱导的EJP幅度刺激（半数有效浓度约为2微摩尔）。环磷酸腺苷的渗透性类似物8-溴环磷酸腺苷（0.1和1毫摩尔）增加了EJP幅度，从而模拟了异丙肾上腺素和福斯可林的作用。8-溴环磷酸腺苷对VSM细胞的静息电位或电流-电压关系无影响，这表明VSM细胞的膜特性未发生改变。8-溴环磷酸鸟苷（1毫摩尔）也增加了EJP幅度，但其促进作用弱于8-溴环磷酸腺苷。8-溴环磷酸鸟苷使VSM膜超极化4毫伏，并降低了输入电阻，推测是由于钾离子电导增加所致。佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA，30-300纳摩尔），一种PK-C的直接激活剂，40分钟后以浓度依赖的方式显著增强了EJP幅度，且不影响VSM细胞的静息电位。根据这些结果，我们认为环磷酸腺苷/PK-A、环磷酸鸟苷/PK-G和DG/PK-C系统可能参与了血管周围神经末梢神经递质释放的调节。然而，不能排除对突触后VSM细胞有某些作用的可能性。
