Independent effects of bradykinin on adenosine 3',5'-monophosphate and prostaglandin E2 metabolism by rabbit renal medulla.
Bradykinin-stimulated increases in renal prostaglandin (PG) synthesis are thought to result in subsequent increases in cAMP content. This study assesses the relationship between bradykinin-stimulated increases in PGE2 and cAMP syntheses in renal inner medullary slices. Bradykinin-mediated increases in cAMP (2 min) preceded those in PGE2 (5 min) synthesis. Forskolin, an activator of adenylate cyclase, increased cAMP, while 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, reduced cAMP. However, neither agent altered bradykinin-stimulated PGE2 synthesis. Aspirin decreased basal and abolished bradykinin-stimulated PGE2 production, but did not alter bradykinin-induced increases in cAMP content. Maximal stimulatory concentrations of 1-methyl-3-isobutylxanthine, a cyclic nucleotide phosphodiesterase inhibitor, and bradykinin were additive in their capacity to increase inner medullary cAMP content. These results suggest that 1-methyl-3-isobutylxanthine and bradykinin increase cAMP by separate mechanisms and that bradykinin increases inner medullary cAMP by a direct effect on the production of that cyclic nucleotide. Bradykinin-mediated increases in cAMP and PGE2 syntheses by renal medullary slices are independent effects of this renally acting hormone.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004224:Diterpenes / Q000494:pharmacology; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011458:Prostaglandins E / Q000378:metabolism*; D011817:Rabbits
D000959:Antihypertensive Agents; D001095:Arachidonic Acids; D004224:Diterpenes; D011458:Prostaglandins E; D005576:Colforsin; D016718:Arachidonic Acid; D000242:Cyclic AMP; D015232:Dinoprostone; D001241:Aspirin; D001920:Bradykinin; D015056:1-Methyl-3-isobutylxanthine