Carbachol mimics phorbol esters in its ability to enhance cyclic GMP production by STa, the heat-stable toxin of Escherichia coli

STa, the heat-stable enterotoxin of Escherichiu coli, stimulates membrane-bound guanylate cyclase in enterocytes, elevates cyclic GMP. and results in intestinal secretion of ions and fluid. Using the T84 colon carcinoma cell line as a model, Weikel et al. reported that phorbol esters enhance STa-stimulated cyclic GMP production by 60 140% [(1990) Infect. Immun. 58, 1402-1407]. In the present report we demonstrate that the acetylcholinc analog carbachol enhanced toxin-stimulated cyclic GMP accumulation in intact T84 cells by 50-100% and that this effect was blocked by 10 μm atropine and 10μM sphingosine. Pertussis toxin treatment of the T84 cells did not affect the subsequent response to carbachol. Carbachol. which elevates intracellular calcium in these cells, may act through protein kinase C to enhance cyclic GMP production.