Effects of prostaglandin f2α and thromboxane a2 analogue on bovine cerebral arterial tone and calcium fluxes

Abstract

We determined sources of activator calcium for prostanoid-induced cerebrova scular constriction by measuring isometric tension and calcium-45 (45Ca) fluxes in bovine middle cerebral arteries. Constriction induced by prostaglandin F2α or the stable thromboxane A2 analogue SQ-26,655 was near-maximally inhibited in calcium-deficient solutions but only partially inhibited by calcium antagonists (10-5 M verapamil or 33 × 10-7 M nifedipine). Studies of45Ca binding at different external Ca2+ concentrations showed that cerebral arteries possess two calcium binding sites, a high-affinity site and a low-affinity site. Each prostanoid significantly increased low-affinity45Ca uptake (external Ca2+ concentration = 1.2 mmol/l) during 5 minutes of45Ca loading; for prostaglandin F2α45Ca uptake increased from 69 to 108 nmol/g and for SQ-26,655, from 78 to 141 nmol/g. The prostanoid-induced increases in low-affinity45Ca uptake were completely abolished by pretreatment with verapamil or nifedipine. Prostaglandin F2α, SQ-26,655, verapamil, and nifedipine had no effect on high-affinity45Ca uptake (external Ca2+concentration=45 μmol/I) or45Ca efflux (after 60 minutes’ preincubation in calcium-deficient media). Prostaglandin F2α and SQ-26,655 each appear to constrict cerebral arteries by two mechanisms: First, by promoting calcium uptake from low-affinity binding sites through receptor-operated channels sensitive to the calcium antagonists, and second, by releasing calcium from depletable internal stores. © 1991 American Heart Association, Inc.