Interactions among prostaglandin receptors.

A single prostaglandin may have multiple effects on the same cell type with each effect showing a different prostaglandin concentration dependence, indicating the presence of separate receptors coupled to different second-messenger systems. The effects may be antagonistic toward each other, suggesting homeostatic control of prostaglandin effects, which may be important in buffering cellular response to elevated prostaglandin levels in inflammation. We have used prostaglandin regulation of cyclic AMP metabolism in platelets and human erythroleukemia (HEL) cells as a model to analyze interactions between stimulatory and inhibitory prostaglandin receptors coupled to adenylate cyclase. Cloning of an EP3 prostaglandin receptor subtype from HEL cells confirmed the presence of an inhibitory receptor distinct from that involved in prostaglandin stimulation of adenylate cyclase.