Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost

The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to ilopros...

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Veröffentlicht in:European journal of pharmacology 1998-09, Vol.356 (2-3), p.215-224
Hauptverfasser: CLAPP, L. H, TURCATO, S, HALL, S, BALOCH, M
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TURCATO, S
HALL, S
BALOCH, M
description The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel blocker, glibenclamide significantly augmented the response to iloprost but not cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by indomethacin, suggesting that iloprost relaxation is counterbalanced by activation of EP1 receptors, in part through a constrictor prostaglandin. We conclude that BKCa channels play an important role in mediating the effects of iloprost and cicaprost and raises the possibility that cyclic AMP-independent pathways might be involved.
doi_str_mv 10.1016/S0014-2999(98)00549-4
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H ; TURCATO, S ; HALL, S ; BALOCH, M</creator><creatorcontrib>CLAPP, L. H ; TURCATO, S ; HALL, S ; BALOCH, M</creatorcontrib><description>The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel blocker, glibenclamide significantly augmented the response to iloprost but not cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by indomethacin, suggesting that iloprost relaxation is counterbalanced by activation of EP1 receptors, in part through a constrictor prostaglandin. 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H</creatorcontrib><creatorcontrib>TURCATO, S</creatorcontrib><creatorcontrib>HALL, S</creatorcontrib><creatorcontrib>BALOCH, M</creatorcontrib><title>Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. 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We conclude that BKCa channels play an important role in mediating the effects of iloprost and cicaprost and raises the possibility that cyclic AMP-independent pathways might be involved.</description><subject>Animals</subject><subject>Antineoplastic Agents - antagonists &amp; inhibitors</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cardiovascular system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Epoprostenol - analogs &amp; derivatives</subject><subject>Epoprostenol - antagonists &amp; inhibitors</subject><subject>Epoprostenol - pharmacology</subject><subject>Guinea Pigs</subject><subject>Hydrazines - pharmacology</subject><subject>Iloprost - antagonists &amp; inhibitors</subject><subject>Iloprost - pharmacology</subject><subject>Isoproterenol - antagonists &amp; inhibitors</subject><subject>Isoproterenol - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Oxazepines - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenylephrine - antagonists &amp; inhibitors</subject><subject>Potassium Channel Blockers</subject><subject>Potassium Channels - drug effects</subject><subject>Potassium Channels - physiology</subject><subject>Prostaglandin Antagonists - pharmacology</subject><subject>Tetraethylammonium - pharmacology</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - antagonists &amp; inhibitors</subject><subject>Vasodilator Agents - pharmacology</subject><subject>Vasodilator agents. 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H</creator><creator>TURCATO, S</creator><creator>HALL, S</creator><creator>BALOCH, M</creator><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19980904</creationdate><title>Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost</title><author>CLAPP, L. H ; TURCATO, S ; HALL, S ; BALOCH, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c265t-c931907f664ad93e1030301ef0d0fe582b2b53d77f6447c3fcd8f7a3a0a9f2583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - antagonists &amp; inhibitors</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cardiovascular system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiology</topic><topic>Epoprostenol - analogs &amp; derivatives</topic><topic>Epoprostenol - antagonists &amp; inhibitors</topic><topic>Epoprostenol - pharmacology</topic><topic>Guinea Pigs</topic><topic>Hydrazines - pharmacology</topic><topic>Iloprost - antagonists &amp; inhibitors</topic><topic>Iloprost - pharmacology</topic><topic>Isoproterenol - antagonists &amp; inhibitors</topic><topic>Isoproterenol - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Oxazepines - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylephrine - antagonists &amp; inhibitors</topic><topic>Potassium Channel Blockers</topic><topic>Potassium Channels - drug effects</topic><topic>Potassium Channels - physiology</topic><topic>Prostaglandin Antagonists - pharmacology</topic><topic>Tetraethylammonium - pharmacology</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - antagonists &amp; inhibitors</topic><topic>Vasodilator Agents - pharmacology</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CLAPP, L. H</creatorcontrib><creatorcontrib>TURCATO, S</creatorcontrib><creatorcontrib>HALL, S</creatorcontrib><creatorcontrib>BALOCH, M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CLAPP, L. H</au><au>TURCATO, S</au><au>HALL, S</au><au>BALOCH, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1998-09-04</date><risdate>1998</risdate><volume>356</volume><issue>2-3</issue><spage>215</spage><epage>224</epage><pages>215-224</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>The role of K+ channels in mediating vasorelaxation induced by two prostacyclin analogues was investigated in guinea-pig aorta. Iloprost caused substantial relaxation of tissues contracted with phenylephrine or 25 mM K+ but not 60 mM K+. In endothelial-denuded tissues, maximal relaxations to iloprost, cicaprost or isoprenaline were inhibited by approximately 40-50% with tetraethylammonium or iberiotoxin, both blockers of large conductance Ca2+-activated K+ (BKCa) channels. In contrast, the response to forskolin, an activator of adenylate cyclase was marginally inhibited by tetraethylammonium. The K(ATP) channel blocker, glibenclamide significantly augmented the response to iloprost but not cicaprost. These effects were largely inhibited by the EP1 receptor antagonist, 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3(4-pyridinyl)propyl]hydrazide, monohydrochloride (SC-51089) and partially by indomethacin, suggesting that iloprost relaxation is counterbalanced by activation of EP1 receptors, in part through a constrictor prostaglandin. We conclude that BKCa channels play an important role in mediating the effects of iloprost and cicaprost and raises the possibility that cyclic AMP-independent pathways might be involved.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>9774252</pmid><doi>10.1016/S0014-2999(98)00549-4</doi><tpages>10</tpages></addata></record>
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subjects Animals
Antineoplastic Agents - antagonists & inhibitors
Antineoplastic Agents - pharmacology
Biological and medical sciences
Calcium - metabolism
Cardiovascular system
Dose-Response Relationship, Drug
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Epoprostenol - analogs & derivatives
Epoprostenol - antagonists & inhibitors
Epoprostenol - pharmacology
Guinea Pigs
Hydrazines - pharmacology
Iloprost - antagonists & inhibitors
Iloprost - pharmacology
Isoproterenol - antagonists & inhibitors
Isoproterenol - pharmacology
Male
Medical sciences
Muscle, Smooth, Vascular - drug effects
Oxazepines - pharmacology
Pharmacology. Drug treatments
Phenylephrine - antagonists & inhibitors
Potassium Channel Blockers
Potassium Channels - drug effects
Potassium Channels - physiology
Prostaglandin Antagonists - pharmacology
Tetraethylammonium - pharmacology
Vasodilation - drug effects
Vasodilator Agents - antagonists & inhibitors
Vasodilator Agents - pharmacology
Vasodilator agents. Cerebral vasodilators
title Evidence that Ca2+-activated K+ channels play a major role in mediating the vascular effects of iloprost and cicaprost
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