Role of prostaglandins in the regulation of intestinal electrolyte transport.

The E prostaglandins (and to a lesser extent PGE2 alpha) stimulate active electrolyte secretion in mammalian small intestine and colon. They do so by stimulating intestinal mucosal adenylate cyclase and thereby increasing cAMP concentration. The diarrheagenic action of the prostaglandins is seen as a side effect of their therapeutic use, in certain hormone-secreting tumors, and in inflammatory lesions of the bowel in which leukocyte infiltrates are the probable sources of prostaglandin excess. Prostaglandins are also normally synthesized by intestinal epithelial cells and appear to play an important role in the physiologic regulation of intestinal fluid transport. In recent in vitro studies, we have shown that addition of arachidonic acid (K 1/2 congruent to 10(-6) M) also stimulates secretion, cAMP accumulation, and PGE2 production in rabbit ileal mucosa. In the continued presence of arachidonate, tachyphylaxis develops: both secretory and cAMP responses have a half-life of about twenty minutes and subsequent additions of arachidonate produce little or no further response. In contrast, PGE2 production continues undiminished. Similar tachyphylaxis develops when PGE2 itself is added. Resensitization following removal of PGE2 is rapid, 50% of the initial sensitivity being restored in 6-7 min. Prostaglandin desensitization has been noted in other cell systems and appears to be exerted on adenylate cyclase.