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• W1509842018 abstract "Background and purpose: The study investigated whether eugenosedin‐A, a 5‐hydroxytryptamine and α / β adrenoceptor antagonist, enhanced delayed‐rectifier potassium (K DR )‐ or large‐conductance Ca 2+ ‐activated potassium (BK Ca )‐channel activity in basilar artery myocytes through cyclic AMP/GMP‐dependent and ‐independent protein kinases. Experimental approach: Cerebral smooth muscle cells (SMCs) were enzymatically dissociated from rat basilar arteries. Conventional whole cell, perforated and inside‐out patch‐clamp electrophysiology was used to monitor K + ‐ and Ca 2+ ‐channel activities. Key results: Eugenosedin‐A (1 μ M ) did not affect the K DR current but dramatically augmented BK Ca channel activity in a concentration‐dependent manner. Increased BK Ca current was abolished by charybdotoxin (ChTX, 0.1 μ M ) or iberiotoxin (IbTX, 0.1 μ M ), but not affected by a small‐conductance K Ca blocker (apamin, 100 μ M ). BK Ca current activation by eugenosedin‐A was significantly inhibited by an adenylate cyclase inhibitor (SQ 22536, 10 μ M ), a soluble guanylate cyclase inhibitor (ODQ, 10 μ M ), competitive antagonists of cAMP and cGMP (Rp‐cAMP, 100 μ M and Rp‐cGMP, 100 μ M ), and cAMP‐ and cGMP‐dependent protein kinase inhibitors (KT5720, 0.3 μ M and KT5823, 0.3 μ M ). Eugenosedin‐A reversed the inhibition of BK Ca current induced by the protein kinase C activator, phorbol myristyl acetate (PMA, 0.1 μ M ). Eugenosedin‐A also prevented BK Ca current inhibition induced by adding PMA, KT5720 and KT5823. Moreover, eugenosedin‐A reduced the amplitude of voltage‐dependent L‐type Ca 2+ current (I Ca,L ), but without modifying the voltage‐dependence of the current. Conclusions and implications: Eugenosedin‐A enhanced BK Ca currents by stimulating the activity of cyclic nucleotide‐dependent protein kinases. Physiologically, this activation would result in the closure of voltage‐dependent calcium channels and thereby relax cerebral SMCs. British Journal of Pharmacology (2007) 152 , 374–385; doi: 10.1038/sj.bjp.0707406 ; published online 13 August 2007" @default.
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• W1509842018 date "2007-10-01" @default.
• W1509842018 modified "2023-10-13" @default.
• W1509842018 title "Activation of BK_Ca channels via cyclic AMP- and cyclic GMP-dependent protein kinases by eugenosedin-A in rat basilar artery myocytes" @default.
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• W1509842018 doi "https://doi.org/10.1038/sj.bjp.0707406" @default.
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