心房利钠肽通过可溶性鸟苷酸环化酶对离体盲肠环形平滑肌细胞的直接抑制作用。

Direct inhibitory effect of atrial natriuretic peptide on isolated caecal circular smooth muscle cells via soluble guanylate cyclase.

作者信息

Akiho H, Chijiiwa Y, Okabe H, Harada N, Nawata H

机构信息

Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Life Sci. 1994;55(16):1293-9. doi: 10.1016/0024-3205(94)90068-x.

DOI:10.1016/0024-3205(94)90068-x

PMID:7934631

Abstract

Atrial natriuretic peptide (ANP) relaxes the vascular smooth muscle via particulate guanylate cyclase. Smooth muscle cells isolated from the caecal circular muscle layer of the guinea pig were used to examine the direct inhibitory effect of ANP on those cells. The role of adenylate cyclase, particulate guanylate cyclase, and soluble guanylate cyclase in the direct inhibitory effect of ANP on contraction of this muscle cell induced by carbachol was investigated. ANP inhibited the contractile response produced by 10(6)M carbachol in a concentration-dependent manner, with an IC50 value of 8nM. An inhibitor of adenylate cyclase (2',5'-dideoxyadenosine) and two inhibitors of particulate guanylate cyclase (HS-142-1, and PMA) had no significant effect on the relaxation produced by ANP. In contrast, an inhibitor of soluble guanylate cyclase (LY83583) significantly and completely inhibited the relaxation produced by ANP. This is the first report demonstrating the direct inhibitory action of ANP on the isolated caecal smooth muscle cells via soluble guanylate cyclase, which differs from the intracellular mechanism responsible for the relaxation of vascular smooth muscle produced by ANP.

摘要

心房利钠肽（ANP）通过颗粒型鸟苷酸环化酶使血管平滑肌舒张。从豚鼠盲肠环肌层分离出的平滑肌细胞用于研究ANP对这些细胞的直接抑制作用。研究了腺苷酸环化酶、颗粒型鸟苷酸环化酶和可溶性鸟苷酸环化酶在ANP对卡巴胆碱诱导的该肌细胞收缩的直接抑制作用中的作用。ANP以浓度依赖的方式抑制10⁻⁶M卡巴胆碱产生的收缩反应，IC50值为8nM。腺苷酸环化酶抑制剂（2',5'-二脱氧腺苷）和两种颗粒型鸟苷酸环化酶抑制剂（HS-142-1和PMA）对ANP产生的舒张作用无显著影响。相反，可溶性鸟苷酸环化酶抑制剂（LY83583）显著且完全抑制了ANP产生的舒张作用。这是首次报道ANP通过可溶性鸟苷酸环化酶对分离的盲肠平滑肌细胞产生直接抑制作用，这与ANP使血管平滑肌舒张的细胞内机制不同。