pH-dependent stimulation by Ca2+ of prostacyclin synthesis in rat aortic rings: effects of drugs and inorganic ions.
Fresh rat aortic rings were incubated in HEPES-buffered salt solutions. Extracellular Ca2+ stimulated the production of prostacyclin (PGI2), as determined by radioimmunoassay of its stable hydrolysis product 6-oxo-prostaglandin F1 alpha. This action of Ca2+ was modified by H+ over the pH range 8.0-6.5. Stimulation by calcium ionophore A23187 was not pH-dependent. In parallel incubations of aortic rings with 45Ca2+, followed by washing in the presence of La3+, tissue uptake of 45Ca2+ increased progressively as extracellular pH was increased from 6.5-8.0. Over this range intracellular pH, estimated by the distribution of [14C]-dimethadione, varied from 5.9-7.4. Stimulation by Ca2+ of PGI2 synthesis was concentration-dependent over the range 0.7-20 mM. The maximum effect was an increase of approx. 4 fold. Nifedipine, but not verapamil or diltiazem, inhibited Ca2+-stimulated PGI2 synthesis. A dihydropyridine compound that activates voltage-dependent Ca2+ channels, Bay K 8644, did not increase PGI2 synthesis. 8-(N, N-diethylamino)-octyl-3,4,5 timethoxybenzoate (TMB-8), an antagonist of intracellular Ca2+ mobilisation, inhibited basal and Ca2+-stimulated PGI2 synthesis to a similar extent. A solution containing 40 mM K+ reduced Ca2+-stimulated PGI2 production. Mg2+ stimulated PGI2 synthesis in a pH-dependent manner but was less potent than Ca2+. Other divalent cations (Mn2+, Ba2+ and Sr2+), and La3+ had little or no effect on basal or Ca2+-stimulated PGI2 synthesis.
Ritter
J M
JM
Frazer
C E
CE
Taylor
G W
GW
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002121:Calcium Channel Blockers; D002412:Cations; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011464:Epoprostenol; D002118:Calcium