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pH‐dependent stimulation by Ca 2+ of prostacyclin synthesis in rat aortic rings: effects of drugs and inorganic ions
Author(s) -
Ritter J.M.,
Frazer C.E.,
Taylor G.W.
Publication year - 1987
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.1476-5381.1987.tb10299.x
Subject(s) - extracellular , chemistry , prostacyclin , stimulation , calcium , verapamil , divalent , intracellular , nifedipine , biochemistry , biophysics , endocrinology , biology , organic chemistry
1 Fresh rat aortic rings were incubated in HEPES‐buffered salt solutions. Extracellular Ca 2+ stimulated the production of prostacyclin (PGI 2 ), as determined by radioimmunoassay of its stable hydrolysis product 6‐oxo‐prostaglandin F 1α . This action of Ca 2+ was modified by H + over the pH range 8.0–6.5. Stimulation by calcium ionophore A23187 was not pH‐dependent. 2 In parallel incubations of aortic rings with 45 Ca 2+ , followed by washing in the presence of La 3+ , tissue uptake of 45 Ca 2+ increased progressively as extracellular pH was increased from 6.5–8.0. Over this range intracellular pH, estimated by the distribution of [ 14 C]‐dimethadione, varied from 5.9‐7.4. 3 Stimulation by Ca 2+ of PGI 2 synthesis was concentration‐dependent over the range 0.7–20 m m . The maximum effect was an increase of approx. 4 fold. 4 Nifedipine, but not verapamil or diltiazem, inhibited Ca 2+ ‐stimulated PGI 2 synthesis. A dihydropyridine compound that activates voltage‐dependent Ca 2+ channels, Bay K 8644, did not increase PGI 2 synthesis. 5 8‐(N, N‐diethylamino)‐octyl‐3,4,5 timethoxybenzoate (TMB‐8), an antagonist of intracellular Ca 2+ mobilisation, inhibited basal and Ca 2+ ‐stimulated PGI 2 synthesis to a similar extent. 6 A solution containing 40 m m K + reduced Ca 2+ ‐stimulated PGI 2 production. Mg 2+ stimulated PGI 2 synthesis in a pH‐dependent manner but was less potent than Ca 2+ . Other divalent cations (Mn 2+ , Ba 2+ and Sr 2+ ), and La 3+ had little or no effect on basal or Ca 2+ ‐stimulated PGI 2 synthesis.