Serotonin receptor-mediated stimulation of bovine smooth muscle cell prostacyclin synthesis and its modulation by platelet-derived growth factor.

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Abstract
Serotonin (5-hydroxytryptamine; 0.5 .mu.M and above) stimulated the synthesis of prostacyclin (as measured by radioimmunoassay of 6-ketoprostaglandin F1.alpha.) by bovine aortic smooth muscle cells in culture. This effect was structurally specific; a similar response was not elicited by the other indoles (tryptophan, n-acetylserotonin, 5-hydroxytryptophan, melatonin, or 5-hydroxyindoleacetic acid) or by the amines phenylephrine, isoproterenol, dopamine or histamine. The response was reversible and was saturable at serotonin concentrations of 10 .mu.M or higher. An increase in prostacyclin synthesis was elicited by the addition of a serotonin agonist, quipazine (1 .mu.M and above), and antagonized by the serotonin receptor blockers cyproheptadine, methysergide, or methiothepin but not by other aminergic receptor-blocking drugs (e.g., phentolamine or propranolol). This effect was selective for cell type because serotonin or quipazine (100 .mu.M) did not increase prostacyclin synthesis by bovine aortic endothelial cells. The addition of platelet-derived growth factor (PDGF) to cultures of smooth muscle cells dramatically enhanced prostacyclin synthesis in response to the coadministration of serotonin. PDGF greatly increased the maximum response to serotonin without altering the half-maximal effective concentration for serotonin. This synergistic interaction was blocked by the addition of a serotonin-receptor blocking agent. Serotonin apparently stimulates smooth muscle prostacyclin synthesis through a specific receptor-mediated mechanism that can be modulated by PDGF.