title: Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.
abstract: Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Guo-Du
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Sumei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Meihua
authors.initials: M
authors.lastname: Qu
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Anesthesiology, College of Medicine, The Ohio State University, Columbus, Ohio; and.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Needleman
authors.affiliation: Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Mikami
authors.affiliation: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio; Jackie.Wood@osumc.edu.
authors.forename: Jackie D
authors.initials: JD
authors.lastname: Wood
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D053818:Chymases / Q000378:metabolism; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000378:metabolism / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D006168:Guinea Pigs; D006636:Histamine Release; D006801:Humans; D007421:Intestine, Small / Q000294:innervation*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000502:physiology; D019899:Paracrine Communication; D018689:Sensory System Agents / Q000494:pharmacology; D013127:Spinal Nerves / Q000378:metabolism / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D013997:Time Factors
chemical_list: D018689:Sensory System Agents; D013373:Substance P; C083294:chymase 2; D053818:Chymases
keywords: functional gastrointestinal disorders; histamine; irritable bowel syndrome; mast cell degranulation; mast cell proteases; visceral pain