Kawai M, Naruse M, Yoshimoto T, Naruse K, Shionoya K, Tanaka M, Morishita Y, Matsuda Y, Demura R, Demura H
Department of Medicine, Tokyo Women's Medical College, Japan.
Endocrinology. 1996 Jan;137(1):42-6. doi: 10.1210/endo.137.1.8536640.
Although atrial and brain natriuretic peptides are well known to be involved in the regulation of cardiovascular and endocrine functions as circulating hormones, the roles of the C-type natriuretic peptide (CNP) remain unknown. We examined the effects of CNP on the secretion of aldosterone and cyclic nucleotides from bovine adrenal zona glomerulosa cells in culture. CNP produced a dose-dependent increase in the basal secretion of cGMP, with an EC50 of 3.8 x 10(-10)M. CNP significantly inhibited the ACTH-induced increase in aldosterone and cAMP in a dose-related manner, with an IC50 of 3.6 x 10(-10)M. Although ACTH itself did not increase cGMP secretion, the addition of CNP elicited a significant increase in cGMP secretion. The effects of CNP on the basal secretion of cGMP and the ACTH-induced secretion of aldosterone were significantly reversed by a nonpeptide natriuretic peptide receptor antagonist, HS-142-1. CNP immunoreactivity was localized in the zona glomerulosa by immunohistochemical staining. In addition, expression of CNP messenger RNA and natriuretic peptide B receptor messenger RNA was demonstrated by RT-PCR in the zona glomerulosa tissue and cells in culture. These findings suggest that CNP is a local factor regulating ACTH-induced aldosterone secretion through a guanylyl cyclase-cGMP pathway.
虽然心房钠尿肽和脑钠尿肽作为循环激素参与心血管和内分泌功能的调节已广为人知，但C型钠尿肽（CNP）的作用仍不清楚。我们研究了CNP对培养的牛肾上腺球状带细胞醛固酮分泌和环核苷酸分泌的影响。CNP使cGMP的基础分泌呈剂量依赖性增加，半数有效浓度（EC50）为3.8×10⁻¹⁰M。CNP以剂量相关方式显著抑制促肾上腺皮质激素（ACTH）诱导的醛固酮和cAMP增加，半数抑制浓度（IC50）为3.6×10⁻¹⁰M。虽然ACTH本身不增加cGMP分泌，但加入CNP可引起cGMP分泌显著增加。非肽类钠尿肽受体拮抗剂HS-142-1可显著逆转CNP对cGMP基础分泌和ACTH诱导的醛固酮分泌的影响。通过免疫组织化学染色，CNP免疫反应性定位于球状带。此外，通过逆转录聚合酶链反应（RT-PCR）在球状带组织和培养细胞中证实了CNP信使核糖核酸（mRNA）和钠尿肽B受体mRNA的表达。这些发现表明，CNP是一种通过鸟苷酸环化酶-cGMP途径调节ACTH诱导的醛固酮分泌的局部因子。
