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Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase


INDOMETHACIN is a potent inhibitor of prostaglandin synthesis1,2, and has been used to demonstrate indirectly the mediation of biological events by prostaglandins. The rationale for this use of indomethacin has been supported when analytical techniques for direct prostaglandin quantitation have been used3,4. There are, however, conflicting data. A role for prostaglandins as the physiological messengers between hormones such as thyrotropin (TSH) and luteinising hormone (LH) and cyclic AMP has been proposed because prostaglandin antagonists inhibit the stimulatory effects of these hormones at their target tissues5,6. A similar role has been proposed in the action of cholera toxin7,8. In both cases, indomethacin failed to prevent the stimulatory effect of these agents on cyclic AMP production, giving support to the opposite view that prostaglandins were not essential intermediates9–11. Paradoxically, indomethacin suppresses, in vivo, thyroid hormone secretion12 and cholera toxin-induced intestinal fluid accumulation13–15. A post-cyclic AMP site of action for indomethacin may explain these discrepancies. To elucidate the role of cyclic AMP-dependent protein kinase and endogenous protein phosphorylation in cholera toxin-induced intestinal secretion16, we have tested the influence of indomethacin on partially purified protein kinase from rabbit ileal mucosa. We report here that indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase and endogenous protein phosphorylation.

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KANTOR, H., HAMPTON, M. Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase. Nature 276, 841–842 (1978).

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