A1 and A2 adenosine receptor activation inhibits and stimulates renin secretion of rat renal cortical slices.
Previous studies by others have demonstrated that exogenous adenosine inhibits renin secretion in vivo. In the present experiments, we studied the effects of three adenosine receptor agonists [N6-cyclohexyladenosine (CHA), 2-chloroadenosine (2-CIA) and 5'-N-ethylcarboxamideadenosine (NECA)] on renin secretion of rat renal cortical slices. The effects were biphasic; submicromolar concentrations inhibited secretion concentration-dependently and the order of potency was CHA greater than 2-CIA greater than NECA. Micromolar and higher concentrations stimulated secretion concentration-dependently and the order of potency was reversed: NECA greater than 2-CIA greater than 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 adenosine receptors. Calcium chelation abolished the inhibitory effect of CHA, suggesting that increased intracellular calcium mediates the inhibitory effect; on the other hand, the inhibitory effect was unaffected by membrane depolarization and calcium channel blockade, suggesting that CHA-induced inhibition is not due to calcium influx through voltage-sensitive calcium channels. Ouabain, vanadate and K-depolarization, all of which are believed to increase intracellular calcium, antagonized CHA- and NECA-stimulated renin secretion, suggesting that the stimulatory effect of these agonists is mediated by decreased intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
Churchill
P C
PC
Churchill
M C
MC
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002118:Calcium / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000145:classification / Q000187:drug effects*; D011983:Receptors, Purinergic; D012083:Renin / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014639:Vanadium; D015762:2-Chloroadenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D005711:Gallopamil; D014638:Vanadates; D004533:Egtazic Acid; D010042:Ouabain; D011189:Potassium Chloride; D013806:Theophylline; D012083:Renin; D000241:Adenosine; D002118:Calcium