PROSTAGLANDIN-E1-INDUCED DESENSITIZATION OF PROSTAGLANDIN-SENSITIVE ADENYLATE-CYCLASE OF CULTURED MAMMALIAN-CELLS - STUDIES WITH BROKEN AND INTACT CELL PREPARATIONS

Prostaglandin E1-induced desensitization of prostaglandin-sensitive adenylate cyclase has been investigated in intact and broken-cell preparations of two cell lines, P388F-36 and PCM1, P388F-36 cells may be characterized by their low intracellular cAMP concentration after exposure to the hormone, whereas PCM1 cells accumulate high concentration of cAMP under similar conditions. Broken-cell preparations from both cell lines exhibit a similar prostaglandin-sensitive adenylate cyclase activity. When the activity is examined after prior exposure of intact cells to hormone, the nature of and extent of desensitization is quite distinct in these two cell lines. In PCM1 cells, desensitization proceeds rapidly to completion with no change in the apparent affinity for prostaglandin E1, whereas in P388F-36, the maximum extent of desensitization is only 30-40%, although a 10-fold decrease in affinity for the hormone is observed. GTP and Gpp(NH)p effects are identical in control and desensitized preparations. These results are discussed in relation to the regulation of adenylate cyclase in the two cell lines. © 1979.