Cross talk among cyclic AMP, cyclic GMP, and Ca(2+)-dependent intracellular signalling mechanisms in brain capillary endothelial cells.
C-type natriuretic peptide and sodium nitroprusside, a nitric oxide donor molecule, induced large increases in cyclic GMP formation in cultured rat brain capillary endothelial cells. Isoproterenol, a potent agonist of adenylate cyclase, potentiated the actions of C-type natriuretic peptide and of sodium nitroprusside. These actions were not observed in the presence of isobutylmethylxanthine and were mimicked by forskolin. Endothelin-1 had no action on basal cyclic GMP levels. It reduced cyclic GMP formation induced by C-type natriuretic peptide and sodium nitroprusside by about 50%. These actions involved an ETA receptor subtype and a Ca(2+)-dependent and protein kinase C-independent mechanism. Finally, increasing cyclic GMP slightly prolonged intracellular Ca2+ transients induced by endothelin-1. The results suggest the presence of extensive cross talk among cyclic AMP, cyclic GMP, and Ca(2+)-dependent mechanisms in endothelial cells of brain microvessels. The relevance of the results to the regulation of the blood-brain barrier permeability is discussed.
Vigne
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Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Université de Nice Sophia Antipolis, Valbonne, France.
Lund
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Frelin
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000494:pharmacology / Q000502:physiology*; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D007425:Intracellular Membranes / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D051381:Rats; D017466:Receptors, Endothelin / Q000145:classification / Q000378:metabolism; D015398:Signal Transduction
D016232:Endothelins; D017466:Receptors, Endothelin; D005576:Colforsin; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine