Effects of prostaglandin F2 alpha 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 (45Ca) fluxes in bovine middle cerebral arteries. Constriction induced by prostaglandin F2 alpha 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 3.3 x 10(-7) M nifedipine). Studies of 45Ca 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-affinity 45Ca uptake (external Ca2+ concentration = 1.2 mmol/l) during 5 minutes of 45Ca loading; for prostaglandin F2 alpha 45Ca 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 45Ca uptake were completely abolished by pretreatment with verapamil or nifedipine. Prostaglandin F2 alpha, SQ-26,655, verapamil, and nifedipine had no effect on high-affinity 45Ca uptake (external Ca2+ concentration = 45 mumol/l) or 45Ca efflux (after 60 minutes' preincubation in calcium-deficient media). Prostaglandin F2 alpha 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.
Wendling
W W
WW
Department of Anesthesiology, Temple University Hospital, Philadelphia, PA 19140.
Harakal
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D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D009994:Osmolar Concentration; D013928:Thromboxane A2 / Q000031:analogs & derivatives*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D005229:Fatty Acids, Monounsaturated; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C032408:SQ 26536; D015237:Dinoprost; D002118:Calcium