Verspohl E J, Bernemann I K
University of Münster, Department of Pharmacology, Germany.
Peptides. 1996;17(6):1023-9. doi: 10.1016/0196-9781(96)00152-0.
ANP increases insulin levels in vivo. Because in vitro an ANP-induced increase in cGMP levels of islets of Langerhans was observed but no simultaneous increase in insulin release, secreted glucagon may be a candidate for this second messenger affected by ANP. The inhibitory effect of glucose on glucagon secretion was pronounced by 1.0 nM ANP at 3.0 mM glucose as well as at 5.6 and 8.3 mM glucose. Because in other tissues cGMP (the specific second messenger of ANP1 inhibits Ca2+ channels, the uptake of 45Ca2+ was investigated. ANP (1.0 nM) inhibited 45Ca2+ uptake, which was nearly completely abolished by a pertussis toxin (PT) pretreatment. The inhibition of 45Ca2+ uptake fits to inhibitory ANP effects on glucagon secretion but does not fit to insulin secretion. The glucagon secretion coupling cascade affected by ANP probably involves an increase in cGMP because 8-Br-cGMP (a membrane-permeable cGMP analogue) also decreased glucagon secretion. ANP(4-23), a truncated form of ANP, which is selective for the ANP clearance receptor, also inhibited glucagon secretion. HS-42-1, a guanylate cyclase receptor antagonist, tended to reverse the effect of ANP on glucagon release. The data indicate that in the presence of ANP, the in vivo homeostasis of glucose, though plasma insulin levels are increased, is not due to an ANP-mediated increase in glucagon secretion; ANP has a complex inhibitory effect on glucagon release. The data further indicate that the ANP-induced inhibition of glucagon secretion probably involves the cGMP system, an inhibition of Ca2+ uptake and the involvement of PT-sensitive G-proteins. Moreover, an involvement of the clearance receptor seems to be likely. ANP is a valuable tool for investigating glucagon secretion from pancreatic islets because paracrine effects of insulin can be excluded.
心钠素（ANP）可在体内增加胰岛素水平。因为在体外观察到ANP可使胰岛的环磷酸鸟苷（cGMP）水平升高，但胰岛素释放却没有同时增加，所以分泌的胰高血糖素可能是受ANP影响的这一第二信使的候选物质。在3.0 mM葡萄糖以及5.6和8.3 mM葡萄糖条件下，1.0 nM的ANP可显著增强葡萄糖对胰高血糖素分泌的抑制作用。由于在其他组织中cGMP（ANP的特异性第二信使）可抑制钙离子通道，因此研究了45Ca2+的摄取情况。ANP（1.0 nM）可抑制45Ca2+摄取，而百日咳毒素（PT）预处理几乎可完全消除这种抑制作用。45Ca2+摄取的抑制与ANP对胰高血糖素分泌的抑制作用相符，但与胰岛素分泌不相符。受ANP影响的胰高血糖素分泌偶联级联反应可能涉及cGMP的增加，因为8-溴-cGMP（一种可透过细胞膜的cGMP类似物）也可降低胰高血糖素分泌。ANP(4-23)是ANP的截短形式，对ANP清除受体具有选择性，它也可抑制胰高血糖素分泌。鸟苷酸环化酶受体拮抗剂HS-42-1倾向于逆转ANP对胰高血糖素释放的作用。数据表明，在存在ANP的情况下，尽管血浆胰岛素水平升高，但体内葡萄糖的稳态并非由于ANP介导的胰高血糖素分泌增加所致；ANP对胰高血糖素释放具有复杂的抑制作用。数据进一步表明，ANP诱导的胰高血糖素分泌抑制可能涉及cGMP系统、对Ca2+摄取的抑制以及PT敏感的G蛋白的参与。此外，清除受体似乎也可能参与其中。ANP是研究胰岛胰高血糖素分泌的一种有价值的工具，因为可以排除胰岛素的旁分泌作用。
