Evaluation of the action of cholinergic agonists and cyclic guanosine monophosphate (c'GMP) on histamine release from purified rat mast cells.

Results from previous studies providing conflicting data regarding the effects of cholinomimetic drugs and cyclic 3',5'-guanosine monophosphate salts (cyclic GMP) upon the release of histamine from various tissues. In the present investigations, highly purified rat peritoneal mast cells were incubated with a wide range of concentrations of carbachol, acetylcholine, and cyclic GMP in the absence and presence of the histamine releasing agents compound 48/80 and concanavalin A (Con A). Neither carbachol nor acetylcholine (10(-13) to 10(-4) M) alone caused rat mast cells to secrete histamine. Furthermore, when these drugs were combined with Con A (Con A 1 and 10 microgram/ml, carbachol 10(-13) to 10(-4) M) and compound 48/80 (compound 48/80 0.2 microgram/ml) acetylcholine 10(-13) to 10(-4) M), no enhancement of histamine release was observed. Cyclic GMP (8-bromo and dibutyryl salts) failed to elicit histamine release from rat mast cells over the concentration range 10(-7) to 10(-3) M. As well, cyclic GMP did not enhance Con A (10 microgram/ml)-induced histamine release. In fact this substance inhibited the release by as much as 15% at 10(-3) M concentrations. The present data suggest that neither cholinomimetic drugs nor cyclic GMP evoked direct release or enhance the release of histamine from purified rat peritoneal mast cells.