C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines:: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in αT3-1 gonadotroph-derived cells
C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines:: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in αT3-1 gonadotroph-derived cells
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DOI：
10.1677/joe.0.1660195
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发表时间：
2000-07-01
影响因子：
4
通讯作者：
McArdle, CA
中科院分区：
文献类型：
--
作者：
Fowkes, RC;Forrest-Owen, W;McArdle, CA
C 型利钠肽 (CNP) 是利钠肽家族的第三个成员，在垂体前叶中发现其组织浓度最高，且位于促性腺激素中。其特定的含有鸟苷酸环化酶的受体 GC-B 也在几种垂体前叶细胞类型上表达，并且 CNP 能有效刺激大鼠垂体细胞培养物和垂体细胞系中的 cGMP 积累。小鼠促性腺激素来源的 α T3-1 细胞系已被证明表达 CNP 以及 GC-B（但不包括 GC-A）受体，表明 CNP 很可能是促性腺激素的自分泌调节剂。比较三种利钠肽（心房利钠肽 (ANP)、B 型利钠肽 (BNP) 和 CNP）对四种垂体细胞系（α T3-1、TtT-GF、AtT-20 和 GH(3)）中 cGMP 积累的影响，我们发现 CNP 在 α T3-1 细胞中最有效。在这些细胞中，CNP 刺激的 cGMP 积累被发现在暴露于 CNP 30 分钟期间脱敏。用 CNP 预处理长达 bh 也会导致 CNP 随后刺激 cGMP 积累的能力显着降低。这种效应是受体特异性的，因为用硝普钠（一氧化氮敏感鸟苷酸环化酶的激活剂）或 ANP 或 BNP 进行预处理，不会导致 CNP 刺激的 cGMP 积累脱敏。用佛波酯激活蛋白激酶 C 也抑制 CNP 刺激的 cGMP 积累，并且在用 CNP 预处理脱敏的细胞中也观察到这种抑制。因此，α T3-1细胞的内源性GC-B受体似乎经历同源和异源脱敏，这些形式的脱敏背后的机制是不同的，并且单独的cGMP升高不足以使GC-B受体脱敏。
C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, has been found at its highest tissue concentrations in the anterior pituitary, where it is localised in gonadotrophs. Its specific guanylyl cyclase containing receptor, GC-B, is also expressed on several anterior pituitary cell types, and CNP potently stimulates cGMP accumulation in rat pituitary cell cultures and pituitary cell lines. The mouse gonadotroph-derived alpha T3-1 cell Line has been shown to express CNP as well as GC-B (but not GC-A) receptors, suggesting that CNP may well be an autocrine regulator of gonadotrophs. Comparing effects of three natriuretic peptides (atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and CNP) on cGMP accumulation in four pituitary cell lines (alpha T3-1, TtT-GF, AtT-20 and GH(3)) we find that CNP is most potent and effective in alpha T3-1 cells. In these cells, CNP-stimulated cGMP accumulation was found to desensitise during a 30 min exposure to CNP. Pretreatment with CNP for up to bh also caused a significant reduction in the ability of CNP to subsequently stimulate cGMP accumulation. This effect was receptor specific, because pretreatment with sodium nitroprusside (an activator of nitric oxide-sensitive guanylyl cyclase), or with ANP or BNP, did not cause desensitisation of CNP-stimulated cGMP accumulation. Protein kinase C activation with phorbol esters also inhibited CNP-stimulated cGMP accumulation and such inhibition was also seen in cells desensitised by pretreatment with CNP. Thus it appears that the endogenous GC-B receptors of alpha T3-1 cells are subject to both homologous and heterologous desensitisation, that the mechanisms underlying these forms of desensitisation are distinct, and that cGMP elevation alone is insufficient to desensitise GC-B receptors.