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.
Hernández
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F
Departamento de Biología Molecular, Universidad Autónoma de Madrid, Spain.
Martínez
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AM
Piedra
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Catalán
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D006633:Histamine Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788; D006632:Histamine; D000242:Cyclic AMP; D007545:Isoproterenol; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D015056:1-Methyl-3-isobutylxanthine