Hormonal dose–response to an adenosine receptor agonist

The effect of various doses of i.p. injection of the adenosine receptor agonist (R)-phenylisopropyladenosine (R-PIA), ranging from nanomolar to micromolar concentrations, on plasma levels of free fatty acids, glucose, insulin, glucagon, ACTH, and corticosterone was examined in 200-g male rats. At the lowest dose of R-PIA (0.005 μmol/kg), a marked decrease in plasma insulin and free fatty acids was observed. This effect on free fatty acids persisted up to the highest concentration of R-PIA (50 μmol/kg). The insulin response showed a similar pattern except at the highest concentration, when the plasma levels were within normal ranges. A 100% increase in plasma glucose was found, but only with doses of 0.5 μmol/kg and above, suggesting an A2 receptor influence, possibly related to the elevation of plasma glucagon observed with the same doses of R-PIA. It has been shown that caffeine, an antagonist of adenosine, stimulates the pituitary–adrenal axis. Surprisingly, it was shown that R-PIA produces the same effect, as evidenced by the marked elevation of both plasma ACTH and corticosterone at concentrations of 0.5 μmol/kg and higher. It is suggested that this centrally mediated effect is due to a primary peripheral action.Key words: adenosine, glucose, free fatty acids, insulin, glucagon, ACTH, corticosterone.