NEUROIMMUNE COMMUNICATION IN THE SUBMUCOUS PLEXUS OF GUINEA-PIG COLON AFTER SENSITIZATION TO MILK ANTIGEN

We investigated electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to beta-lactoglobulin in guinea pigs sensitized by ingestion of milk. Microelectrodes were used to record electrical and synaptic behavior in neurons from milk-sensitized and nonsensitized age-matched animals during exposure to beta-lactoglobulin. Neurons in sensitized animals were hyperexcitable. Application of the histamine H-2 antagonist cimetidine-reversed the hyperexcitability, suggesting endogenously released histamine as one of the responsible factors. Antigenic exposure suppressed stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potentials (EPSPs). This was blocked by the selective histamine H-3 antagonist burimamide. Suppression of the EPSPs resulted from presynaptic inhibition of acetylcholine release. Increased neuronal excitability and suppression of synaptic transmission was only found in milk-sensitized intestine, not in the intestine from age-matched nonsensitized animals. We concluded that signaling from mucosal mast cells to the enteric nervous system is important in colonic defense against antigenic threats. Histamine is a paracrine messenger in the communication network.