Action of adenosine on cyclic 3',5'-nucleotides in glomeruli

Recent in vivo studies indicated that adenosine has a profound effect on glomerular dynamics and renal circulation. Because its effect in nonrenal tissues is frequently mediated by adenosine 3',5'-cyclic monophosphate (cAMP), we examined adenosine's effect on cyclic nucleotides in rat kidney. Incubation of tissue slices from renal cortex or medulla with 0.1 mM adenosine resulted in marginal or no increase in cAMP. In isolated glomeruli, adenosine caused a marked and dose-dependent (10(-6) to 10(-4) M) increase in cAMP accumulation. Inosine, a deaminated metabolite of adenosine, had no effect on cAMP levels in glomeruli. No distinct effect of adenosine on cAMP was observed in cortical tubules under the same testing conditions. An increase in cAMP levels in glomeruli elicited by adenosine was blocked by theophylline, a known inhibitor of adenosine receptors. In contrast, theophylline enhanced rather than decreased the stimulation of cAMP accumulation in glomeruli by serotonin. Dipyridamole, a proposed inhibitor of cellular uptake of adenosine, did not inhibit but rather enhanced cAMP accumulation in glomeruli in response to adenosine. In the present experiments adenosine did not influence guanosine 3',5'-cyclic monophosphate levels in either glomeruli or other tested preparations of renal tissue. These results provide the first experimental evidence that adenosine stimulates cAMP accumulation in glomeruli and suggest that this effect is probably due to action on the adenosine receptor on the cell surface. Our observations raise the possibility that some of the effects of adenosine in glomerular cells may be mediated via cAMP accumulation.