Independent mechanisms for bradykinin-mediated prostaglandin E2 and cyclic GMP syntheses in rabbit renal inner medulla slices.
The relationship between bradykinin-mediated prostaglandin (PG)E2 and cyclic GMP syntheses was investigated using rabbit renal inner medullary slices. Media PGE2 and slice cyclic GMP content were determined by specific radioimmunoassays. Effects of the time of incubation, the cyclic nucleotide phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine, the prostaglandin synthesis inhibitor aspirin and calcium exclusion were examined. Maximal bradykinin-mediated increases in cyclic GMP preceded increases in PGE2 synthesis. 1-Methyl-3-isobutylxanthine increased basal and bradykinin-mediated cyclic GMP content 6- to 10-fold, but reduced basal and bradykinin-mediated PGE2 synthesis. 1-Methyl-3-isobutylxanthine did not alter arachidonic acid-mediated PGE2 synthesis and did not uncover an arachidonic acid-dependent increase in the cyclic GMP content. Aspirin completely inhibited basal, bradykinin- and arachidonic acid-mediated PGE2 synthesis but did not alter basal or bradykinin-dependent cyclic GMP production. Neither exogenous cyclic GMP nor dibutyryl cyclic GMP altered basal or bradykinin-mediated increases in PGE2 synthesis. Exclusion of calcium from the media resulted in reduced basal synthesis of both PGE2 and cyclic GMP and prevented the increases caused by bradykinin. Arachidonic acid increases in PGE2 were not altered by calcium exclusion. The results indicate that bradykinin-dependent renal medullary slice synthesis of cyclic GMP and PGE2 are not dependent upon one another. However, they both require calcium. Some of the physiological effects of bradykinin on renal function may be mediated by cyclic GMP and others by PGs.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000494:pharmacology; D015232:Dinoprostone; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D013997:Time Factors
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D006152:Cyclic GMP; D015232:Dinoprostone; D001241:Aspirin; D001920:Bradykinin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine