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.
Omar
R
R
Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1QJ, Cambridge, UK.
Bottrill
F E
FE
Hiley
C R
CR
White
R
R
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