Jang E K, Davidson M M, Crankshaw D, Haslam R J
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Eur J Pharmacol. 1993 Dec 21;250(3):477-81. doi: 10.1016/0014-2999(93)90038-j.
Atriopeptin II and isoproterenol acted synergistically to inhibit the phenylephrine-induced contraction of aortic smooth muscle from Wistar-Kyoto (WKY) rats. Thus, a weakly inhibitory concentration of atriopeptin II (10 nM) caused a 5-fold decrease in the IC50 of isoproterenol from 169 nM to 32 nM, whereas a low concentration of isoproterenol (100 nM) increased the maximum inhibition attributable to atriopeptin II from 43% to 74%. Atriopeptin II (10 nM) increased the cGMP found in aortic smooth muscle and approximately doubled the accumulation of cAMP caused by isoproterenol. The results suggest that cGMP, formed by the action of atriopeptin II on receptor guanylyl cyclase (GC-A), may inhibit aortic cyclic nucleotide phosphodiesterase type III (PDE III) and that an increased accumulation of cAMP then mediates the observed synergism.
心房肽II和异丙肾上腺素协同作用，抑制苯肾上腺素诱导的Wistar-Kyoto（WKY）大鼠主动脉平滑肌收缩。因此，低抑制浓度的心房肽II（10 nM）使异丙肾上腺素的IC50降低了5倍，从169 nM降至32 nM，而低浓度的异丙肾上腺素（100 nM）使心房肽II的最大抑制作用从43%提高到74%。心房肽II（10 nM）增加了主动脉平滑肌中的cGMP，并使异丙肾上腺素引起的cAMP积累量增加了约一倍。结果表明，心房肽II作用于受体鸟苷酸环化酶（GC-A）形成的cGMP可能抑制主动脉III型环核苷酸磷酸二酯酶（PDE III），然后cAMP积累增加介导了观察到的协同作用。
