Bell-shaped curves for prostaglandin-induced modulation of adenylate cyclase: two mutually opposing effects

Abstract

Each of the natural prostanoid is at least one order of magnitude more potent for its specific receptor (DP, EP, FP, IP and TP) than any of the other prostanoids. However, they are able to interact also with one or more of the other classes of prostanoid receptors. The concentration–response curves for modulation of adenylate cyclase activity in rabbit mesenteric artery smooth muscle cells by different prostaglandins are not always monotonic, i.e. simple sigmoidal curves in logarithmic scale, but they are often biphasic. Prostacyclin, iloprost and prostaglandin E 1 showed a convex bell-shaped curve, i.e. adenylate cyclase activity is stimulated at lower concentrations and inhibited at higher concentrations, while the curve of prostaglandin E 2 showed a concave bell-shaped curve, i.e. adenylate cyclase is inhibited at lower concentrations and stimulated at higher concentrations. By selectively inhibiting one of the transduction mechanisms present in mesenteric smooth muscle cells, we have demonstrated that the observed responses to these prostanoids are likely due to two mutually opposing effects. Thus, the data previously published by our laboratory on a prostacyclin analog, 5( Z)-carbacyclin, might be reinterpreted more correctly in the light of this new possibility.