Evidence for different purinergic receptors for ATP and ADP in rabbit kidney and heart.

ATP and ADP stimulated the release of specific prostaglandin products from the perfused rabbit kidney heart. The two nucleotides produced the same qualitative profile of prostaglandin products. In kidney, prostaglandin E2 was the major product, whereas in heart 6-keto prostaglandin F1 alpha and prostaglandin E2 predominated. ATP was a slightly more potent than ADP. ATP administered into the perfused heart to kidney was rapidly hydrolyzed to ADP and AMP. The prostaglandin E2 generating activity of ATP was increased 6-10 fold when ATP was given together with AMP-PCP or AMP-PNP which competitively inhibit the activity of vascular ATPase. Thus, the rapid hydrolysis of ATP reduces its agonistic activity for prostaglandin release. ATP and ADP administered together at maximal stimulating doses produced an additive response for prostaglandin E2 release. These results and the results of tachyphylaxis experiments indicate that ATP and ADP interact independently with different types of purinergic receptors.