Endocrinology, Vol 132, 524-529, Copyright © 1993 by Endocrine Society

ARTICLES

Endothelin receptor subtypes are coupled to adenylate cyclase via different guanyl nucleotide-binding proteins in vasculature

S Eguchi, Y Hirata, T Imai and F Marumo
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.

We have studied whether endothelin (ET) isopeptides have any effects on adenylate cyclase activity via different guanyl nucleotide-binding proteins (G-proteins) in cultured rat vascular smooth muscle cells (VSMC) and bovine endothelial cells (EC). Northern blot analysis clearly demonstrated gene expression of ETA receptors in VSMC and ETB receptors in EC. ET-1 dose-dependently (10(-9)-10(-6) M) stimulated cAMP formation in VSMC, whose effect was inhibited completely by ETA receptor antagonist (BQ-123) but not by indomethacin or quinacrine. The ET-1-induced cAMP formation was additive with isoproterenol but not with cholera toxin. In contrast, ET-3 and ETB receptor agonist (BQ- 3020) dose-dependently (10(-9)-10(-6) M) inhibited forskolin-stimulated cAMP formation in EC, whose effect was completely abolished by pertussis toxin. Cholera toxin ADP ribosylated 45- and 52-kilodalton proteins in VSMC, whereas pertussis toxin ADP ribosylated the 41- kilodalton protein in EC. These data suggest that, in addition to phospholipase C via Gq, ETA and ETB receptor subtypes are functionally coupled to adenylate cyclase, possibly via Gs in VSMC and Gi in EC, respectively.

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