Rashed H M, Nair B G, Patel T B
Department of Pharmacology, University of Tennessee, Memphis 38163.
Arch Biochem Biophys. 1992 Nov 1;298(2):640-5. doi: 10.1016/0003-9861(92)90460-e.
Recently we reported the presence of both the guanylyl cyclase-linked (116 kDa) and the ANF-C (66 kDa) atrial natriuretic peptide receptors in the rat liver. Since ANF 103-125 (atriopeptin II) stimulates cGMP production in livers and because cGMP has previously been shown to mimic the actions of cAMP in regulating hepatic carbohydrate metabolism, studies were performed to investigate the effects of atriopeptin II on hepatic glycolysis and gluconeogenesis. Additionally, employing analogs of atrial natriuretic hormone [des-(Q116, S117, G118, L119, G120) ANF 102-121 (C-ANF) and des-(C105,121) ANF 104-126 (analog I)] which bind only the ANF-C receptors, the role of the ANF-C receptors in the hepatic actions of atriopeptin II was evaluated. In perfused livers of fed rats atriopeptin II, but not C-ANF and analog I, inhibited hepatic glycolysis and stimulated glucose production. Moreover, analog I did not alter the ability of atriopeptin II to inhibit hepatic glycolysis. Atriopeptin II, but not C-ANF and analog I, also stimulated cGMP production in perfused rat livers. Furthermore, while atriopeptin II inhibited the activity ratio of pyruvate kinase by 30%, C-ANF did not alter hepatic pyruvate kinase activity. Finally, in rat hepatocytes, atriopeptin II stimulated the synthesis of [14C]glucose from [2-14C]pyruvate by 50% and this effect of atriopeptin II was mimicked by the exogenously supplied cGMP analog, 8-bromo cGMP. Thus atriopeptin II increases hepatic gluconeogenesis and inhibits glycolysis, in part by inhibiting pyruvate kinase activity, and the effects of atriopeptin II are mediated via activation of guanylyl cyclase-linked ANF receptors which elevate cGMP production.
最近我们报道了大鼠肝脏中存在鸟苷酸环化酶连接型（116 kDa）和心钠素C型（66 kDa）心房利钠肽受体。由于心钠素103 - 125（心房肽II）能刺激肝脏中cGMP的产生，且此前已证明cGMP在调节肝脏碳水化合物代谢方面可模拟cAMP的作用，因此开展了研究以探讨心房肽II对肝脏糖酵解和糖异生的影响。此外，使用仅与心钠素C型受体结合的心房利钠激素类似物[去（Q116，S117，G118，L119，G120）心钠素102 - 121（C - ANF）和去（C105，121）心钠素104 - 126（类似物I）]，评估了心钠素C型受体在心房肽II肝脏作用中的作用。在喂食大鼠的灌注肝脏中，心房肽II而非C - ANF和类似物I抑制肝脏糖酵解并刺激葡萄糖生成。此外，类似物I并未改变心房肽II抑制肝脏糖酵解的能力。心房肽II而非C - ANF和类似物I也能刺激灌注大鼠肝脏中cGMP的产生。此外，虽然心房肽II使丙酮酸激酶的活性比率降低了30%，但C - ANF并未改变肝脏丙酮酸激酶的活性。最后，在大鼠肝细胞中，心房肽II使[2 - 14C]丙酮酸生成[14C]葡萄糖的合成增加了50%，且外源性提供的cGMP类似物8 - 溴cGMP可模拟心房肽II的这种作用。因此，心房肽II增加肝脏糖异生并抑制糖酵解，部分是通过抑制丙酮酸激酶活性实现的，且心房肽II的作用是通过激活鸟苷酸环化酶连接型心钠素受体介导的，该受体可提高cGMP的产生。
