Groome J R, Watson W H
Department of Zoology, University of New Hampshire, Durham 03824.
J Neurobiol. 1987 Sep;18(5):417-31. doi: 10.1002/neu.480180504.
The role of cyclic nucleotides as intracellular second messengers mediating the excitatory chronotropic and inotropic actions of octopamine (OCT) and dopamine (DA) on the neurogenic Limulus heart was investigated. Tissue levels of cAMP, but not cGMP, were significantly increased in isolated cardiac ganglia and cardiac muscle following 10 min exposure to 10(-5) M OCT or 10(-5) M DA. In both tissues, OCT elicited larger increases in cAMP than did DA. Amine-induced cAMP accumulation in the cardiac ganglion and in the cardiac muscle was prevented by the alpha-adrenergic blocker phentolamine. The adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX produced amine-like chronotropic and inotropic effects when applied to the isolated heart preparation. However, the kinetics of the responses differed for the two agents. Additional pharmacological agents (RO-20-1724, papaverine, SQ 20,009, and 8-parachloro-phenylthio cAMP) also had amine-like effects but to a lesser extent. The chronotropic, but not inotropic, effects of OCT and DA were potentiated in the presence of IBMX. These data suggest that a cAMP-dependent mechanism underlies the excitatory effects of the neuromodulators OCT and DA on the Limulus heart.
研究了环核苷酸作为细胞内第二信使介导章鱼胺(OCT)和多巴胺(DA)对神经源性鲎心脏的正性变时和变力作用的角色。在分离的心脏神经节和心肌中,暴露于10(-5) M OCT或10(-5) M DA 10分钟后,cAMP的组织水平显著升高,而cGMP未升高。在这两种组织中,OCT引起的cAMP升高幅度大于DA。心脏神经节和心肌中胺诱导的cAMP积累被α-肾上腺素能阻滞剂酚妥拉明阻止。腺苷酸环化酶激活剂福斯高林和磷酸二酯酶抑制剂异丁基甲基黄嘌呤应用于分离的心脏标本时产生类似胺的变时和变力作用。然而,两种药物的反应动力学不同。其他药理剂(RO-20-1724、罂粟碱、SQ 20,009和8-对氯苯硫基cAMP)也有类似胺的作用,但程度较小。在异丁基甲基黄嘌呤存在下,OCT和DA的变时作用(而非变力作用)增强。这些数据表明,cAMP依赖性机制是神经调节剂OCT和DA对鲎心脏兴奋作用的基础。