Indomethacin and inhibition of protein kinase reactions

Abstract

Indomethacin, an inhibitor of prostaglandin biosynthesis, is useful in studies aimed at understanding the metabolism and physiological function of prostaglandins¹. A recent report² showing that indomethacin at 10^–7 M potently inhibits the cyclic AMP-dependent protein kinases (cAMP-PrK) from ileal mucosa in the presence or absence of cyclic AMP, suggests how indomethacin may antagonize prostaglandin action on ileal mucosa. It also suggests that indomethacin might be useful in studying the properties and functions of protein kinase reactions. Inhibitors of prostaglandin biosynthesis, such as sodium salicylate and acetylsalicylate, at concentrations near 10^–2 M, have been shown to inhibit bovine diaphragm protein kinase only in the presence of cAMP, while stimulating it in the absence of cAMP³. We report here that complete inhibition of cAMP-PrKs by indomethacin requires a concentration of 10^–3 M and is not tissue-specific, and that the effect of indomethacin is concentration dependent above 2 × 10^–4 M for the cAMP-dependent, and above 10^–3 M for cAMP-independent PrKs. These results contrast previous ones².