Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels.
The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (KATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl)amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino]adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 microM), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 microM prostaglandin F2 alpha. Sodium nitroprusside (SNP; 1 nM-10 microM) and KATP-channel activator, pinacidil (10 nM-10 microM), also produced similar vasodilatory responses. Glyburide, a KATP-channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that KATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.
Makujina
S R
SR
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Olanrewaju
H A
HA
Mustafa
S J
SJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials; D010496:Pericardium / Q000502:physiology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D006146:Guanidines; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide