Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture.
1. 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.
Department of Pharmacy, School of Medicine, The University of Tokushima, Kuramoto, Japan.
H
H
Houchi
M
M
Yoshizumi
K
K
Tsuchiya
M
M
Hirose
T
T
Kitagawa
T
T
Kujime
E
E
Shimizu
Y
Y
Niwa
K
K
Minakuchi
T
T
Tamaki
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D019332:Endothelin-1 / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D002395:Catecholamines; D019332:Endothelin-1; D017466:Receptors, Endothelin; D019831:Sodium-Calcium Exchanger; D009569:Nitric Oxide; D012964:Sodium; D006152:Cyclic GMP; D002118:Calcium