Effects of Prostaglandin ¥2a and Thromboxane A2 Analogue on Bovine Cerebral Arterial Tone and Calcium Fluxes

We determined sources of activator calcium for prostanoid-induced cerebrovascular constriction by measuring isometric tension and calcium-45 ("Ca) fluxes in bovine middle cerebral arteries. Constriction induced by prostaglandin F^ 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~ M verapamil or 33xlO~ M nifedipine). Studies of ^Ca binding at different external Ca concentrations showed that cerebral arteries possess two calcium binding sites, a high-affinity site and a low-affinity site. Each prostanoid significantly increased low-affinity ^Ca uptake (external Ca concentration = 1.2 mmol/l) during 5 minutes of '"Ca loading; for prostaglandin F ^ ^Ca 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-affinity ^Ca uptake were completely abolished by pretreatment with verapamil or nifedipine. Prostaglandin F^ , SQ-26,655, verapamil, and nifedipine had no effect on high-affinity ^Ca uptake (external Ca concentration=45 /umol/l) or ^Ca efflux (after 60 minutes' preincubation in calcium-deficient media). Prostaglandin F ^ 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. (Stroke 1991;22:66-72)