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Relaxation of canine gallbladder to nerve stimulation involves adrenergic and non‐adrenergic non‐cholinergic mechanisms
Author(s) -
Alcón S.,
Morales S.,
Camello P. J.,
Salido G. M.,
Miller S. M.,
Pozo M. J.
Publication year - 2001
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1046/j.1365-2982.2001.00286.x
Subject(s) - vasoactive intestinal peptide , guanethidine , endocrinology , medicine , chemistry , atropine , nitric oxide , nitric oxide synthase , adrenergic , cholinergic , stimulation , receptor , neuropeptide
Electrical field stimulation (EFS) of dog gallbladder strips induced a frequency‐dependent contractile response followed by an off‐relaxation that was turned into a pure inhibitory response after atropine pretreatment. Guanethidine reduced the atropine‐induced relaxing responses, so an adrenergic mechanism can partially account for the nerve‐mediated gallbladder relaxation. However, guanethidine pretreatment also revealed a nonadrenergic noncholinergic (NANC) relaxation induced by EFS, which was frequency independent. NANC relaxations were reduced by L ‐arginine methyl ester ( L ‐NAME, 100 μmol L –1 ), a nitric oxide synthase inhibitor ( D ‐p‐Cl‐Phe6, Leul7; 10 μmol L –1 ), a vasoactive intestinal peptide (VIP) receptor antagonist, and an inhibitor of haem oxygenase, (copper protoporphyrin IX; CuPP‐IX; 10 μmol L –1 ), suggesting that nitric oxide (NO), VIP and carbon monoxide (CO), respectively, are released in response to EFS. Immunoreactivities for haem oxygenase‐2 (HO‐2) and VIP, and histochemical staining for NADPH diaphorase were observed in nerve cell bodies and fibres, demonstrating the presence of CO, VIP and NO as putative NANC neurotransmitters in dog gallbladder. These data support the hypothesis that NO, VIP and CO contribute to NANC relaxation of the canine gallbladder.