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Functional evidence that ATP or a related purine is an inhibitory NANC neurotransmitter in the mouse jejunum: study on the identity of P2X and P2Y purinoceptors involved
Author(s) -
De Man Joris G,
De Winter Benedicte Y,
Seerden Tom C,
De Schepper Heiko U,
Herman Arnold G,
Pelckmans Paul A
Publication year - 2003
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.0705536
Subject(s) - apamin , ppads , endocrinology , medicine , purinergic receptor , tetrodotoxin , suramin , p2y receptor , agonist , channel blocker , receptor , nitroarginine , enteric nervous system , neurotransmission , chemistry , biology , adenosine , potassium channel , nitric oxide synthase , calcium , nitric oxide
Conflicting views exist on whether ATP is a neurotransmitter in the enteric nervous system. We investigated the role of ATP in enteric transmission in circular muscle strips of the mouse jejunum. On PGF 2 α ‐precontracted muscle strips and in the presence of atropine and guanethidine, electrical field stimulation (EFS, 1–8 Hz) of nonadrenergic noncholinergic (NANC) nerves induced transient relaxations that were abolished by the nerve‐conductance blocker tetrodotoxin. The NO synthase blocker L ‐nitroarginine ( L ‐NOARG) partially inhibited the NANC relaxations to EFS, but fast‐twitch relaxations to EFS were still observed in the presence of L ‐NOARG. In the presence of L ‐NOARG, ATP, the P2X receptor agonist αβ MeATP and the P2Y receptor agonist ADP β S relaxed jejunal muscle strips. Tetrodotoxin did not affect the relaxation to ATP and ADP β S, but inhibited that to αβ MeATP. The L ‐NOARG‐resistant NANC relaxations to EFS were almost abolished by apamin, a blocker of small‐conductance Ca 2+ activated K + channels, and by suramin and PPADS, blockers of P2 purinoceptors. Relaxations to ATP were almost abolished by apamin and suramin but not affected by PPADS. Desensitisation of αβ MeATP‐sensitive P2X receptors, the P2X receptor blocker Evans blue and the P2X 1,2,3 receptor blocker NF 279 inhibited the L ‐NOARG‐resistant NANC relaxations to EFS and that to αβ MeATP without affecting the relaxation to ADP β S. Brilliant blue G, a P2X 2,5,7 receptor blocker, did not affect the relaxations to EFS. Desensitisation of P2Y receptors and MRS 2179, a P2Y 1 receptor blocker, virtually abolished the L ‐NOARG‐resistant NANC relaxations to EFS and the relaxation to ADP β S without affecting the relaxation to αβ MeATP. Dipyridamole, an adenosine uptake inhibitor, or theophylline and 8‐phenyltheophylline, blockers of P1 and A1 purinoceptors, respectively, did not affect the purinergic NANC relaxations to EFS. Our results suggest that ATP or a related purine acts as an inhibitory NANC neurotransmitter in the mouse jejunum, activating P2 but not P1 purinoceptors. Relaxations to the purinergic NANC neurotransmitter mainly involve P2Y receptors of the P2Y 1 subtype that are located postjunctionally. Purinergic NANC neurotransmission also involves P2X receptors, most likely of the P2X 1 and P2X 3 subtype, located pre‐ and/or postjunctionally.British Journal of Pharmacology (2003) 140 , 1108–1116. doi: 10.1038/sj.bjp.0705536