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, α2- or 5-hydroxytryptamine4 (5-HT4-) receptors.
Circular muscle strips, without mucosa, were incubated with [3H]-choline to incorporate [3H]-acetylcholine into the cholinergic transmitter stores. The basal and electrically-induced release of tritium and [3H]-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 (S1 and S2: 40 V, 1 ms, 4 Hz) and drugs were added before S2.
The NO synthase inhibitor L-NG-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 α2-adrenoceptor agonist UK-14,304 (10−5 M) significantly inhibited the electrically-evoked release of [3H]-acetylcholine, and this was prevented by the α2-adrenoceptor antagonist rauwolscine (2×10−6 M).
The 5-HT4-receptor agonist prucalopride (3×10−7 M) significantly enhanced the electrically-evoked release of [3H]-acetylcholine, and the 5-HT4-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 [3H]-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 α2-adrenoceptors, and stimulated via presynaptic 5-HT4-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