Interaction of cyclic AMP modulating agents with levcromakalim in the relaxation of rat isolated mesenteric artery.
The effect of cyclic AMP modulating agents on levcromakalim-induced relaxation was investigated in myograph-mounted rat mesenteric arteries. Forskolin (adenylyl cyclase activator), dibutyryl cyclic AMP (protein kinase A activator) and 5'-N-ethylcarboxamidoadenosine (NECA; adenosine receptor agonist) all potentiated the vasorelaxant effects of levcromakalim. The modulatory and relaxant effects of dibutyryl cyclic AMP, NECA and forskolin were sensitive to the protein kinase A inhibitor, Rp-cAMPS. However, relaxation to these three agents was unaffected by the K(ATP) inhibitor, glibenclamide. Dibutyryl cyclic AMP and NECA also caused levcromakalim to induce relaxation in the sub-nanomolar concentration range, however, this effect was Rp-cAMPS- and glibenclamide-insensitive. These results suggest that cyclic AMP modulating agents modulate K(ATP), even though this channel does not contribute to their relaxant effects.
Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, UK.
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Omar
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Bottrill
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Hiley
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White
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D013873:Thionucleotides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D019830:Adenosine-5'-(N-ethylcarboxamide); D003994:Bucladesine; D000242:Cyclic AMP; D008729:Methoxamine; C047983:1,9-dideoxyforskolin; D005905:Glyburide