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On the inhibition of prostanoid formation by SK&F 96365, a blocker of receptor‐operated calcium entry
Author(s) -
Leis Hans J.,
Zach Doris,
Huber Evelyn,
Ziermann Laszlo,
Gleispach Helmut,
Windischhofer W.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17181.x
Subject(s) - arachidonic acid , chemistry , calcium , endocrinology , thromboxane a2 , biochemistry , medicine , stimulation , thromboxane receptor , prostaglandin , receptor , biology , enzyme , organic chemistry
1 The proposed blocker of receptor‐operated calcium channels, SK&F 96365 was shown to inhibit formation of prostaglandin E 2 in two osteoblast‐like cell lines, MC3T3‐E1 and UMR‐106 in a dose‐dependent manner at an IC 50 of 3–4 μ m . 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 (IC 50 = 4 μ m ). 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.