Endothelin inhibits histamine-induced cyclic AMP accumulation in bovine brain vessels

We have studied whether endothelin isopeptides have any effects on histamin e-induced cyclic AMP in [H-3]adenine-prelabeled brain vessels isolated from bovine brain. Basal levels of [H-3]cyclic AMP were enhanced by histamine i n a concentration-dependent manner (EC50 = 1.1 +/- 0.3 mu M). Endothelin-l inhibited histamine-elicited [H-3]cyclic AMP generation with an IC50 value of 3 +/- 2.5 nM. Sarafotoxin 6c, an ET-B receptor agonist, had no effect. E T-1 inhibition of histamine-induced [H-3]cyclic AMP was reversed by the ET- A receptor antagonist BQ-123 while the ET-B receptor antagonist BQ-788 had no effect. The levels of [H-3]cyclic AMP induced by isoprenaline were not a ltered by endothelin-l. Taken together, these results show that endothelins modulate the actions of histamine on the blood-brain barrier, probably by type A endothelin receptors. (C) 2000 Academic Press.