Abstract

Evidence is presented that brief trypsin treatment of intact normal rat kidney cells significantly increases the intracellular accumulation of cyclic AMP in response to added prostaglandin E 1 (PGE 1) and (−)-isoproterenol. Trypsin exhibits a concentration-dependent enhancement of hormone-stimulated accumulation of cyclic AMP in intact normal rat kidney cells, with maximal stimulation (two- to threefold) observed with 25 μg/ml trypsin. The trypsin stimulatory effect is rapid, with optimal enhancement noted within 6 to 8 min after protease addition. The extent of stimulation is not altered with increasing PGE 1 concentration. Trypsin, by itself, elicits only a 30 to 50% increase in basal cyclic AMP levels. These results suggest that trypsin might act on the external cell surface to modulate hormonal responsiveness, perhaps by eliminating a GTP inhibitory effect on the normal rat kidney adenylate cyclase system.

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