5-HT(3) receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro.
Exogenously applied tachykinins produce no measurable electrophysiological responses in the somata of vagal afferent neurons [nodose ganglion neurons (NGNs)] isolated from naive guinea pigs. By contrast, after in vitro antigen challenge of nodose ganglia from guinea pigs immunized with chick ovalbumin, approximately 60% (53 of 89) of NGNs were depolarized an average of 13 +/- 1.2 mV by substance P (SP; 100 nM; n = 53). Receptor antagonists and enzyme inhibitors were utilized to screen a number of mast cell-derived mediators for their role in the uncovering or "unmasking" of functional tachykinin receptors after antigen challenge. Two chemically distinct 5-hydroxytryptamine-3-receptor antagonists significantly reduced the percentage of NGNs displaying depolarizing SP responses. Treatment with Y-25130 (1 or 10 microM) or tropisetron (1 microM) 15 min before and during antigen challenge reduced the percentage of SP-responsive neurons to approximately 20 and approximately 15% respectively. These results suggest that activation of 5-hydroxytryptamine-3 receptors plays an integral role in the unmasking of functional tachykinin receptors after specific antigen challenge of nodose ganglia. The mediator(s) underlying tachykinin-receptor unmasking in the remainder of the NGNs has yet to be characterized. However, it does not appear to be histamine, prostanoids, or peptidoleukotrienes.
Moore
Kimberly A
KA
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Oh
Eun Joo
EJ
Weinreich
Daniel
D
D000818:Animals; D000941:Antigens / Q000276:immunology; D002645:Chickens; D004594:Electrophysiology; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology; D007114:Immunization; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D009443:Neuritis / Q000378:metabolism*; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D009620:Nodose Ganglion / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D011453:Prostaglandins / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D018039:Receptors, Tachykinin / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism*
D000941:Antigens; D015289:Leukotrienes; D011453:Prostaglandins; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D006632:Histamine; D010047:Ovalbumin