Adrenergic stimulation of prostacyclin production in the rat tail artery. II. The role of calcium.
This investigation studied the role of extracellular and intracellular calcium in the stimulation of prostacyclin (PGI2) production by norepinephrine (NE) in the rat tail artery in vitro. Incubation of the artery in zero calcium medium inhibited the response to NE as well as the response to the calcium ionophore A23187. Increasing the extracellular calcium concentration had no effect on basal or NE-stimulated PGI2 (measured by radioimmunoassay of the stable metabolite, 6-keto-PGF1 alpha). Several different calcium entry blocking drugs had a partial inhibitory effect on the NE response, but it was noted that the dihydropyridine derivatives, nifedipine and nimodipine, also decreased the stimulatory effect of added exogenous arachidonic acid (AA). This effect on AA conversion was also seen with W-7, a calcium-calmodulin inhibitor, and with TMB-8, an inhibitor of intracellular calcium mobilization. However, two phenothiazine calmodulin inhibitors, trifluoperazine and pimozide, did not affect AA conversion and were effective in reducing the stimulatory response to NE. Trifluoperazine, particularly at a high dose of 10(-4) M, had an independent stimulatory effect on PGI2 production in this tissue. The data suggests that many of the antagonist probes of extracellular-intracellular calcium metabolism may have variable effects on more than one point in the prostaglandin synthetic pathway. Nevertheless, the results are consistent with the hypothesis that NE stimulates PGI2 in the rat tail artery by activation of a calcium-calmodulin dependent phospholipase and that at least some of the calcium is of extracellular origin.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D016718:Arachidonic Acid; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D002118:Calcium; D009638:Norepinephrine