title: Modulation of prostacyclin biosynthesis by calcium entry blockers and extracellular calcium.
abstract: The influence of variations in the availability of extracellular Ca2+ and of Ca2+-entry blockers on prostacyclin production by mesothelial cells in culture was studied. The Ca2+-entry blockers nifedipine and verapamil suppressed the basal, as well as the thrombin-, bradykinin-, and ionophore A23187-stimulated biosynthesis by about 50-60%, but high concentrations were required and the inhibition was never complete. Basal prostacyclin formation was unaffected by a Ca2+-poor buffer, but showed 50% reduction in the Ca2+-free buffer. Although the thrombin-stimulated prostacyclin formation was not significantly influenced by a Ca2+-poor or a Ca2+-free buffer, prostacyclin release stimulated by A23187 and bradykinin was diminished in the presence of these modified incubation media; the reduction of bradykinin stimulated biosynthesis was rather small (30%). These results suggest that the Ca2+ from intracellular stores is sufficient for half maximal stimulation of the phospholipases involved in the biosynthetic pathway of prostacyclin and that--depending on the nature of the stimulus--different phospholipases are activated with varying requirements for free Ca2+.
authors.forename: V J
authors.initials: VJ
authors.lastname: Van de Velde
authors.forename: R M
authors.initials: RM
authors.lastname: Van den Bossche
authors.forename: H
authors.initials: H
authors.lastname: Bult
authors.forename: A G
authors.initials: AG
authors.lastname: Herman
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D011464:Epoprostenol / Q000096:biosynthesis*; D008564:Membrane Potentials; D010537:Peritoneum / Q000378:metabolism*; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D013917:Thrombin; D001920:Bradykinin; D002118:Calcium