内皮素-1刺激培养的牛肾上腺嗜铬细胞中依赖钠的钙外流。

Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture.

Houchi H, Yoshizumi M, Tsuchiya K, Hirose M, Kitagawa T, Kujime T, Shimizu E, Niwa Y, Minakuchi K, Tamaki T

Department of Pharmacy, School of Medicine, The University of Tokushima, Kuramoto, Japan.

Br J Pharmacol. 1998 Sep;125(1):55-60. doi: 10.1038/sj.bjp.0702047.

Abstract

The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10(-7) M) significantly increased intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells preloaded with 45Ca2+ in a concentration-dependent manner (10(-9)-10(-7) M). This stimulatory effect was inhibited by ET(B) receptor antagonist BQ788, but not by ET(A) receptor antagonist BQ123. Selective ET(B) receptor agonists Suc-[Glu9, Ala11.5]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the cells. 3. ET-1, Suc-[Glu9 Ala11.15]-ET-1 and SRTX increased the level of cyclic GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide (NO) level in the cells. The stimulatory effects by which ET- increases NO level and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a competitive inhibitor of NO synthase. 4. The 45Ca2+ efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5. These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+ efflux through the activation of NO synthase in cultured bovine adrenal chromaffin cells.

摘要

研究了内皮素（ET）-1对培养的牛肾上腺嗜铬细胞Ca2+外流的影响。ET-1（10^(-7) M）显著增加细胞内游离Ca2+水平（[Ca2+]i）、45Ca2+摄取及细胞内儿茶酚胺分泌。2. ET-1以浓度依赖性方式（10^(-9)-10^(-7) M）刺激预先加载45Ca2+的细胞中45Ca2+外流。这种刺激作用被ET(B)受体拮抗剂BQ788抑制，但不被ET(A)受体拮抗剂BQ123抑制。选择性ET(B)受体激动剂Suc-[Glu9, Ala11.5]-ET-1和蝎毒素S6c（SRTX）也刺激细胞中45Ca2+外流。3. ET-1、Suc-[Glu9 Ala11.15]-ET-1和SRTX增加肾上腺嗜铬细胞中环鸟苷酸水平。ET-1诱导细胞中一氧化氮（NO）水平升高。ET-1增加NO水平和45Ca2+外流的刺激作用被NO合酶竞争性抑制剂NG-单甲基-L-精氨酸乙酸盐（L-NMMA）抑制。4. ET-1刺激的45Ca2+外流被细胞外Na+剥夺抑制，但不被Ca2+剥夺抑制。5. 这些结果表明，ET-1通过激活培养的牛肾上腺嗜铬细胞中的NO合酶刺激细胞外Na+依赖性Ca2+外流。