Effect of adenosine and its analogues on calcium influx in coronary artery.
In the present study, we have investigated the changes in calcium influx during the relaxing responses to adenosine and its analogues. Calcium-45 influx was measured in bovine coronary artery rings in the presence of prostaglandin F2 alpha (10(-5) M) and KCl (50 and 100 mM). Prostaglandin F2 alpha and KCl caused increases in calcium influx. Prostaglandin F2 alpha produced a further contraction when added to rings maximally contracted with KCl (100 mM or higher), suggesting two different mechanisms for prostaglandin F2 alpha- and KCl-induced contractions. Similarly, a greater calcium influx was observed when prostaglandin F2 alpha was mixed with KCl (50 or 100 mM). At all the concentrations tested, adenosine and its analogues [5'-(N-ethyl-carboxamidoadenosine, NECA; N6-(L-2-phenylisopropyl)adenosine, L-PIA] significantly inhibited prostaglandin F2 alpha-induced increases in calcium influx. However, only higher concentrations of adenosine, NECA, and L-PIA inhibited 100 mM KCl-induced calcium influx. Previous treatment with 8-phenyltheophylline blocked the inhibitory actions of adenosine, NECA, and L-PIA on calcium influx. The inhibition of calcium influx by adenosine, NECA, and L-PIA correlated well with their relaxing ability in the presence of prostaglandin F2 alpha. The data suggest that prostaglandin F2 alpha-induced calcium influx was more sensitive to the action of adenosine and its analogues than the calcium influx induced by high K+ depolarization.
Ramagopal
M V
MV
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Mustafa
S J
SJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology
D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D011189:Potassium Chloride; D015237:Dinoprost; D000241:Adenosine; D002118:Calcium