6 The Riddle of Cholinergic Histamine Release from Mast Cells

This chapter discusses the riddle of cholinergic histamine release from mast cells. The activity of histamine (2-(4-imidazolyl)ethylamine) is discovered in the course of an investigation on ergot, showing that its extracts, the synthetic substance, and the base produced by splitting off carbon dioxide from histidine (by bacterial action or by chemical means), produced, in minute dose, tonic contraction of the uterus. The activity of acetylcholine is also identified in certain specimens of ergot and its extracts, with an action that appeared to be of the muscarinic type. The cholinergic system is clearly separated from the histaminergic system in terms of biosynthetic pathways, storage, release, receptor-mediated effects, and the termination of the physiological actions. A link between the cholinergic system and tissue histamine stores has been established by a variety of experimental evidence, showing that parasympathetic nerve stimulation or the use of cholinergic agonists produces an enhancement of antigen-induced release of histamine from sensitized tissues and the secretion of histamine from tissues and isolated cells, even in the absence of previous sensitization. If such a relationship between the parasympathetic nervous system and one of the major autacoids (histamine) are established, two significant objectives would be reached: (a) to place histamine in a more physiological context and (b) to gain some insight into certain diseases (urticaria, asthma, ulcerative colitis, Chron's disease, and coeliac disease) in which an interaction between the two systems is suspected. The chapter describes the state of knowledge on the interaction between cholinergic and histaminergic systems.