No abstract

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.

The present study was an attempt to characterize the adenosine receptor in human coronary arteries, and to establish the dependence of the relaxations mediated by this receptor on a functional endothelium. Human coronary arteries were obtained from organ donors. Adenosine and its analogs (5'-N-ethyl-carboxamido-adenosine, NECA; N6-L-phenylisopropyladenosine, L-PIA; 2-chloroadenosine, CAD), all inhibited the contraction induced by 25 mmol/l KCl in a concentration-dependent manner and the order of potency was found to be: NECA greater than CAD greater than L-PIA greater than adenosine. These relaxations were antagonized by 8-phenyltheophylline (8PT). At higher concentrations of KCl, the relaxations were attenuated. In rings which relaxed in response to endothelium-dependent relaxing agents (bradykinin and A23187), NECA and CAD produced relaxations similar to those produced in rings which did not show endothelium-dependent responses. The results suggest that the coronary adenosine receptor (probably A2) mediates relaxations which may not be dependent on the relaxing function of the endothelium.

No abstract

We have investigated the mechanism of adenosine-induced relaxation in relation to its effects on intracellular organelles in Triton X-100- and saponin-skinned bovine coronary arteries. In intact coronary arteries, high K+ and prostaglandin F2 alpha caused sustained contractions, whereas caffeine produced transient contractions. Triton X-100 treatment abolished these contractions. However, Triton X-100-skinned coronary arteries were responsive to added free calcium. There was no significant difference between calcium concentration-response curves obtained in the absence and presence of adenosine (50 microM). Unlike Triton X-100, in saponin-skinned arteries, caffeine produced transient contractions but high K+ and prostaglandin F2 alpha did not. Adenosine had no effect on caffeine-induced contractions in saponin-skinned coronary arteries. These data suggest that adenosine had no direct inhibitory effect on either the contractile apparatus or calcium release from sarcoplasmic reticulum in coronary arteries.