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Inhibitory pathways in the circular muscle of rat jejunum
Author(s) -
Vanneste Gwen,
Robberecht Patrick,
Lefebvre Romain A
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705918
Subject(s) - apamin , vasoactive intestinal peptide , endocrinology , medicine , guanethidine , pertussis toxin , purinergic receptor , neurotransmission , inhibitory postsynaptic potential , chemistry , tetrodotoxin , ppads , adenosine , receptor antagonist , antagonist , potassium channel , receptor , biology , stimulation , neuropeptide , g protein
Conflicting data have been reported on the contribution of nitric oxide (NO) to inhibitory neurotransmission in rat jejunum. Therefore, the mechanism of relaxation and contribution to inhibitory neurotransmission of NO, adenosine 5′‐triphosphate (ATP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating peptide (PACAP) was examined in the circular muscle of Wistar–Han rat jejunum. Mucosa‐free circular muscle strips were precontracted with methacholine in the presence of guanethidine and exposed to electrical field stimulation (EFS) and exogenous NO, ATP, VIP and PACAP. All stimuli induced reduction of tone and inhibition of phasic motility. Only electrically induced responses were sensitive to tetrodotoxin (3 × 10 −6 M ). NO (10 −6 –10 −4 M )‐induced concentration‐dependent relaxations that were inhibited by the soluble guanylyl cyclase inhibitor 1H‐[1,2,4]‐oxadiazolo‐[4,3‐ a ]‐quinoxalin‐1‐one (ODQ; 10 −5 M ) and the small conductance Ca 2+ ‐activated K + ‐channel blocker apamin (APA; 3 × 10 −8 M ). Relaxations elicited by exogenous ATP (10 −4 –10 −3 M ) were inhibited by the P2Y purinoceptor antagonist reactive blue 2 (RB2; 3 × 10 −4 M ), but not by APA and ODQ. The inhibitory responses evoked by 10 −7 M VIP and 3 × 10 −8 M PACAP were decreased by the selective PAC 1 receptor antagonist PACAP 6–38 (3 × 10 −6 M ) and APA. The VPAC 2 receptor antagonist PG99‐465 (3 × 10 −7 M ) reduced relaxations caused by VIP, but not those by PACAP, while the VPAC 1 receptor antagonist PG97‐269 (3 × 10 −7 M ) had no influence. EFS‐induced relaxations were inhibited by the NO‐synthase inhibitor N ω ‐nitro‐ L ‐arginine methyl ester (3 × 10 −4 M ), ODQ and APA, but not by RB2, PG97‐269, PG99‐465 and PACAP 6–38 . These results suggest that NO is the main inhibitory neurotransmitter in the circular muscle of Wistar–Han rat jejunum acting through a rise in cyclic guanosine monophosphate levels and activation of small conductance Ca 2+ ‐dependent K + channels.British Journal of Pharmacology (2004) 143 , 107–118. doi: 10.1038/sj.bjp.0705918