The interaction of cholinomimetics, peptides and compounds 48/80 on histamine secretion from the mast cell.

The mechanism of selective, non-immunological histamine release from mast cells, caused by various endogenous substances, is not clearly understood. Since in vivo experiments indicate that the local control of secretory cells is influenced by acetylcholine and peptides, we investigated whether the secretion of histamine is similarly regulated in the mast cell. Experiments were performed with peritoneal cavity cell suspensions (PCS) of the rat. The endogenous polypeptide substance P, compound 48/80 and a non-hydrolysable cholinomimetic agonist, carbachol, were used. The concentrations of the drugs were kept low to avoid non-specific histamine release caused by morphological damage of mast cells. It was found that: (1) carbachol (2 X 10(-5) M) did not release histamine from PCS, (2) substance P (6.5 X 10(-6) M) released histamine and this effect was increased by the addition of carbachol (2 X 10(-5) M); the effect of carbachol was inhibited by atropine , (3) carbachol (2 X 10(-5)M) did not increase histamine release caused by compound 48/80 (0.02 micrograms/ml). From these experiments it may be concluded that activation of peptidergic receptor(s) can cause histamine release from mast cells and that muscarinic agents may be involved in the regulation of the(se) receptor(s).