A1 AND A2 ADENOSINE RECEPTOR ACTIVATION INHIBITS AND STIMULATES RENIN SECRETION OF RAT RENAL CORTICAL SLICES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (3) , 589-594
Abstract
Previous studies demonstrated that exogenous adenosine inhibits renin secretion in vivo. The effects of 3 adenosine receptor agonists [N6-cyclohexyladenosine (CHA), 2-chloroadenosine (2-CIA) and 5''-N-ethylcarboxamideadenosine (NECA)] on renin secretion of rat renal cortical slices were studied. The effects were biphasic; submicromolar concentrations inhibited secretion concentration-dependently and the order of potency was CHA > 2-CIA > NECA. Micromolar and higher concentrations stimulated secretion concentration-dependently and the order of potency was reversed: NECA > 2-CIA > CHA. These results are consistent with the hypothesis that activation of A1 and A2 adenosine receptors produces inhibition and stimulation of secretion, respectively. Theophylline antagonized both the inhibitory effect of low concentrations of CHA and the stimulatory effect of higher concentrations, providing additional evidence for mediation by activation of cell-surface receptors. Ca chelation abolished the inhibitory effect of CHA, suggesting that increased intracellular Ca mediated the inhibitory effect; the inhibitory effect was unaffected by membrane depolarization and Ca channel blockade, suggesting that CHA-induced inhibition is not due to Ca influx through voltage-sensitive Ca channels. Ouabain, vanadate and K-depolarization, all of which seemingly increase intracellular calcium, antagonized CHA- and NECA-stimulated renin secretion, suggesting that the stimulatory effect of these agonists is mediated by decreased intracellular Ca. Activation of adenosine receptors can stimulate as well as inhibit renin secretion, the effects are independent of the adenosine-induced changes in renal hemodynamics observed in vivo and changes in intracellular Ca concentration most likely account for the changes in renin secretion.