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Store-operated channels (SOC) and store-operated [Ca.sup.2+] entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type [Ca.sup.2+] ([Ca.sup.2+.sub.L]) channels are thought to be fully responsible for agonist-induced [Ca.sup.2+] influx and vasoconstriction. We present evidence that SOC and their activation via a [Ca.sup.2+] -independent phospholipase [A.sub.2] ([iPLA.sub.2])-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular [Ca.sup.2+] in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) [Ca.sup.2+] and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a [Ca.sup.2.sub.L+] inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and [Ca.sup.2.sub.L+] channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of [iPLA.sub.2][beta] totally inhibited PE-induced [Ca.sup.2+] influx and constriction in cerebral, mesenteric, and carotid arteries, whereas [K.sup.+]-induced [Ca.sup.2+] influx and vasoconstriction mediated by [Ca.sup.2+.sub.L] channels were not affected. Thus [iPLA.sub.2]-dependent activation of SOC is crucial for agonist-induced [Ca.sup.2+] influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of [Ca.sup.2+] stores, nonselective SOC are activated via an [iPLA.sub.2]-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of [Ca.sup.2+.sub.L] channels and lead to [Ca.sup.2+] entry and vasoconstriction. store-operated calcium entry; smooth muscle cells; constriction

Store-operated channels (SOC) and store-operated Ca2+ entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type Ca2+ (CaL2+) channels are thought to be fully responsible for agonist-induced Ca2+ influx and vasoconstriction. We present evidence that SOC and their activation via a Ca2+-independent phospholipase A2 (iPLA2)-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular Ca2+ in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) Ca2+ and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a CaL2+ inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and CaL2+ channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of iPLA2β totally inhibited PE-induced Ca2+ influx and constriction in cerebral, mesenteric, and carotid arteries, whereas K+-induced Ca2+ influx and vasoconstriction mediated by CaL2+ channels were not affected. Thus iPLA2-dependent activation of SOC is crucial for agonist-induced Ca2+ influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of Ca2+ stores, nonselective SOC are activated via an iPLA2-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of Ca2+ channels and lead to Ca2+ entry and vasoconstriction. [ABSTRACT FROM AUTHOR]