Abstract
1. The proposed blocker of receptor-operated calcium channels, SK&F 96365 was shown to inhibit formation of prostaglandin E2 in two osteoblast-like cell lines, MC3T3-E1 and UMR-106 in a dose-dependent manner at an IC50 of 3-4 microM. Inhibition was observed with various stimuli (arachidonic acid, bradykinin and calcium ionophore A23187). 2. This effect was also observed in human platelets, where SK&F 96365 dose-dependently blocked thromboxane biosynthesis and formation of 12-hydroxy-heptadecatrienoic acid after stimulation with arachidonic acid (IC50 = 4 microM). 3. The compound had no effect on 12-hydroxy-eicosatetraenoic acid production by human platelets. Additionally, linoleic acid oxidation by soybean 15-lipoxidase was not impaired by SK&F 96365. The results thus provide evidence for cyclo-oxygenase inhibition by SK&F 96365 at concentrations used to block receptor-operated calcium influx.