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Modulation of cyclic 3′5′‐adenosine monophosphate in cultured renal (MDCK) cells by endogenous prostaglandins
Author(s) -
Hassid Aviv
Publication year - 1983
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041160306
Subject(s) - endogeny , bradykinin , prostaglandin , prostaglandin e , prostaglandin e2 , endocrinology , medicine , chemistry , adenosine , prostaglandin e1 , second messenger system , prostaglandin antagonist , cyclic adenosine monophosphate , intracellular , biology , biochemistry , receptor
Abstract Cyclic AMP plays an important regulatory role in transport activity and proliferation of renal MDCK cells. This observation and the ability of MDCK cells to synthesize prostaglandins provided the impetus to assess the hypothesis that endogenous prostaglandins modulate cyclic AMP concentrations in MDCK cells. Three dissimilar cyclo‐oxygenase inhibitors: acetylsalicylate, 5, 8, 11, 14‐eicosatetraynoate, and meclofenamate significantly decreased cellular cyclic AMP levels and inhibited basal prostaglandin E 2 synthesis. On the other hand, three dissimilar stimulators of prostaglandin synthesis: bradykinin, Ca 2+ ‐ionophore A23187 and arachidonate, increased cellular cyclic AMP levels, and stimulated prostaglandin E 2 synthesis. Acetylsalicylate inhibited the bradykinin‐ and A23187‐evoked increases of cyclic AMP as well as that of prostaglandin E 2 synthesis. Prostaglandin E 2 , the major prostaglandin synthesized by MDCK cells, dose‐dependently increased cAMP levels when added exogenously. Acetylsalicylate did not significantly affect increases of cyclic AMP evoked by exogenous prostaglandin E 2 , documenting that acetylsalicylate inhibited cellular cyclic AMP levels by decreasing endogenous prostaglandin synthesis, rather than by a direct effect on cyclic AMP metabolism. Other prostaglandins synthesized by MDCK cells, i.e., prostaglandins I 2 , 6‐keto‐F 1α , and F 2α added exogenously did not significantly affect MDCK cyclic AMP levels, suggesting that they were probably ineffective as endogenous modulators of cyclic AMP. Moreover, endogenous prostaglandin E 2 appeared four‐ to eightfold more potent as a stimulator of cyclic AMP levels than exogenous prostaglandin E 2 . The results support the concept that prostaglandin E 2 is an endogenous cellular mediator that acts between an extracellular effector such as bradykinin and a second endogenous mediator of hormone action: cyclic AMP.