Microcalorimetric studies on the effect of adenosine receptor agonists and xanthine derivatives on overall metabolism in human platelets.

Abstract

The direct overall metabolic effects of drugs acting on adenosine receptors in human platelets were evaluated using a sensitive microcalorimetric method. Adenosine induced a concentration-dependent increase in the heat production rate at concentrations above 100 microM. The adenosine uptake inhibitor, dipyridamole (3 microM) did not modify the effect of adenosine. Two putative adenosine receptor agonists were tested: NECA (5-N-ethyl carboxamide adenosine) and PIA (L-N6-phenylisopropyl-adenosine). NECA induced, at significantly lower concentrations than adenosine, an enhanced heat production rate. Concentrations above 1 mM had no effect. PIA, on the other hand, invariably induced a reduction in the heat production rate already at a concentration of 100 microM. The two xanthine derivatives enprofylline (25 microM) and theophylline (100 microM) were tested at concentrations found during antiasthmatic therapy. Neither had any thermogenic effect by themselves nor showed any significant modification of the heat production rate induced by adenosine (300 microM). These results indicate that adenosine and NECA increase human platelet metabolism, whereas PIA has an opposite effect. The proposed adenosine receptor antagonists enprofylline and theophylline were without effects. This microcalorimetric study gives new insights into the complex nature of adenosine mechanisms in a human test system and indicates that the thermogenic effect of adenosine is unrelated to adenosine receptors.