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Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach
Author(s) -
Leclere Pascal G,
Lefebvre Romain A
Publication year - 2002
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.0704471
Subject(s) - acetylcholine , endocrinology , medicine , guanethidine , chemistry , rauwolscine , cholinergic , vasoactive intestinal peptide , muscarinic acetylcholine receptor , agonist , physostigmine , atropine , nitroarginine , stimulation , prazosin , receptor , nitric oxide synthase , biology , antagonist , nitric oxide , neuropeptide
This study investigates whether the cholinergic neurones, innervating the human proximal stomach, can be modulated by nitric oxide (NO) or vasoactive intestinal polypeptide (VIP), or via presynaptic muscarinic, α 2 ‐ or 5‐hydroxytryptamine 4 (5‐HT 4 ‐) receptors. Circular muscle strips, without mucosa, were incubated with [ 3 H]‐choline to incorporate [ 3 H]‐acetylcholine into the cholinergic transmitter stores. The basal and electrically‐induced release of tritium and [ 3 H]‐acetylcholine were analysed in a medium containing guanethidine (4×10 −6 M ), hemicholinium‐3 (10 −5 M ), physostigmine (10 −5 M ) and atropine (10 −6 M ). Tissues were stimulated twice for 2 min (S 1 and S 2 : 40 V, 1 ms, 4 Hz) and drugs were added before S 2 . The NO synthase inhibitor L ‐N G ‐nitroarginine methyl ester (3×10 −4 M ) and the NO donor sodium nitroprusside (10 −5 M ), as well as VIP (10 −7 M ) did not influence the basal release nor the electrically‐evoked release. The α 2 ‐adrenoceptor agonist UK‐14,304 (10 −5 M ) significantly inhibited the electrically‐evoked release of [ 3 H]‐acetylcholine, and this was prevented by the α 2 ‐adrenoceptor antagonist rauwolscine (2×10 −6 M ). The 5‐HT 4 ‐receptor agonist prucalopride (3×10 −7 M ) significantly enhanced the electrically‐evoked release of [ 3 H]‐acetylcholine, and the 5‐HT 4 ‐receptor antagonist SB204070 (10 −9 M ) prevented this. When atropine (10 −6 M ) was omitted from the medium and added before the second stimulation, it significantly increased the release of [ 3 H]‐acetylcholine. These results suggest that the release of acetylcholine from the cholinergic neurones, innervating the circular muscle in the human proximal stomach, can be inhibited via presynaptic muscarinic auto‐receptors and α 2 ‐adrenoceptors, and stimulated via presynaptic 5‐HT 4 ‐receptors. No evidence for modulation by NO or VIP was obtained.British Journal of Pharmacology (2002) 135 , 135–142; doi: 10.1038/sj.bjp.0704471