Pituitary adenylate cyclase-activating polypeptide stimulates cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99–126) secretion from cultured neonatal rat myocardiocytes

Iris Bäsler , Michaela Kuhn , Werner Müller , Wolf-Georg Forssmann
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引用次数: 17

Abstract

It has been reported that the highly homologous neuropeptides pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP) exert similar cardiovascular effects in vivo. In the present study we compared the effects of these neuropeptides on myocardial cyclic AMP content and the release of immunoreactive CDD/ANP-(99–126) (atrial natriuretic peptide). In cultured neonatal rat cardiomyocytes PACAP and VIP evoke concentration-dependent increases in intracellular cyclic AMP content but responses to VIP are markedly less. PACAP stimulates the release of CDD/ANP-(99–126) in a concentration-dependent manner with a threshold concentration of 1 nM, and up to a 6-fold increase in basal secretion at 1 μM PACAP. In contrast, VIP had no effect on the release of CDD/ANP. Pretreatment of cells with the competitive PACAP-antagonist, PACAP-6-38 (1 μM), significantly reduces the effects of PACAP on intracellular cyclic AMP and on CDD/ANP-(99–126) secretion and abolishes the effects of VIP on cyclic AMP. Pretreatment with VIP-receptor antagonist (1 μM) prevents the cyclic AMP-responses to VIP while increases in cyclic AMP as well as stimulation of CDD/ANP-(99–126) release by PACAP are not affected. It is concluded that both neuropeptides directly influence cardiac myocytes through an increase in intracellular cyclic AMP. Release of CDD/ANP-(99–126) by PACAP may be involved in the decrease in blood pressure that follows intravenous administration of this peptide. The higher potency of PACAP to induce cyclic AMP synthesis, its stimulating effect on the release of CDD/ANP-(99–126) and the finding that the VIP-receptor antagonist inhibits responses to VIP but not to PACAP suggest that PACAP activates cardiac myocytes through a PACAP-specific receptor.

垂体腺苷酸环化酶激活多肽刺激培养的新生大鼠心肌细胞分泌心舒张素/心房利钠肽(CDD/ANP-(99-126))
据报道,高度同源的脑垂体腺苷酸环化酶激活肽(PACAP)和血管活性肠多肽(VIP)在体内发挥类似的心血管作用。在本研究中,我们比较了这些神经肽对心肌环AMP含量和免疫反应性CDD/ANP-(99-126)(心房利钠肽)释放的影响。在培养的新生大鼠心肌细胞中,PACAP和VIP引起细胞内环AMP含量的浓度依赖性增加,但对VIP的反应明显减弱。PACAP刺激CDD/ANP-(99-126)以浓度依赖的方式释放,阈值浓度为1 nM,在1 μM PACAP下,基础分泌增加6倍。相比之下,VIP对CDD/ANP的释放没有影响。竞争性PACAP拮抗剂PACAP-6-38 (1 μM)预处理细胞可显著降低PACAP对细胞内环AMP和CDD/ANP-(99-126)分泌的影响,并消除VIP对环AMP的影响。VIP受体拮抗剂(1 μM)预处理可阻止环AMP对VIP的反应,而PACAP对环AMP的增加和CDD/ANP-(99-126)释放的刺激不受影响。由此得出结论,这两种神经肽通过增加细胞内环AMP直接影响心肌细胞。PACAP释放CDD/ANP-(99-126)可能参与静脉注射这种肽后血压的降低。PACAP诱导环AMP合成的效能更高,对CDD/ANP-释放的刺激作用(99-126),以及VIP受体拮抗剂抑制VIP反应而不抑制PACAP的发现,表明PACAP通过PACAP特异性受体激活心肌细胞。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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