Effects of adenosine analogues on tension and cytosolic Ca2+ in porcine coronary artery.
This study evaluates the relaxing effects of adenosine analogues in relation to intracellular free Ca2+ concentration ([Ca2+]i) in porcine coronary artery. Changes in muscle tension and [Ca2+]i were measured simultaneously using the fluorescent Ca2+ indicator, fura 2-acetoxymethyl ester. The ratio of fluorescence due to excitation at 340 nm to that at 380 nm reflects [Ca2+]i. Increased tension of the porcine coronary artery contracted with prostaglandin F2 alpha (PGF2 alpha, 20 microM) was accompanied by increased [Ca2+]i. The adenosine analogues, N6-cyclopentyladenosine (CPA), 2-chloroadenosine (CAD), and 2-[m-(carboxyethyl)-phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988) produced a concentration-dependent (10(-8)-10(-4) M) reduction of [Ca2+]i and tension with a maximum relaxation of approximately 96% and a [Ca2+]i decrease of 88% at a concentration of 10(-4) M. The order of potency for relaxation was CAD > CGS-22988 = CPA. Adenosine receptor antagonists (8-phenyltheophylline, 10(-6) M; CGS-15943, 10(-5) M) shifted the agonist-mediated relaxation and [Ca2+]i curve to the right in a parallel fashion. In Ca(2+)-free buffer, PGF2 alpha (20 microM)-induced contraction was significantly reduced (75%). PGF2 alpha also caused a transient increase in [Ca2+]i that later was reduced below the resting level. The order of potency for relaxation for adenosine analogues in Ca(2+)-free buffer was found to be CAD = CGS-22988 > CPA. All curves were shifted to the right in the presence of receptor antagonists. These results indicate that adenosine receptor-mediated changes in [Ca2+]i and relaxation in porcine coronary smooth muscle are at least partly independent of extracellular Ca2+.
Olanrewaju
H A
HA
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
Mustafa
S J
SJ
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D002021:Buffers; D005456:Fluorescent Dyes; D058915:Purinergic P1 Receptor Antagonists; C049925:fura-2-am; D000241:Adenosine; D002118:Calcium; D016257:Fura-2