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

We have studied whether endothelin isopeptides have any effects on histamine-induced cyclic AMP in [(3)H]adenine-prelabeled brain vessels isolated from bovine brain. Basal levels of [(3)H]cyclic AMP were enhanced by histamine in a concentration-dependent manner (EC(50) = 1.1 +/- 0.3 microM). Endothelin-1 inhibited histamine-elicited [(3)H]cyclic AMP generation with an IC(50) value of 3 +/- 2.5 nM. Sarafotoxin 6c, an ET-B receptor agonist, had no effect. ET-1 inhibition of histamine-induced [(3)H]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 [(3)H]cyclic AMP induced by isoprenaline were not altered by endothelin-1. Taken together, these results show that endothelins modulate the actions of histamine on the blood-brain barrier, probably by type A endothelin receptors.