American Journal of Physiology. Gastrointestinal and Liver Physiology vol:300 issue:5 pages:G782-G794
Aims: To explore the myenteric mechanisms of control of human esophageal motility and the effect of nitrergic and non-nitrergic neurotransmitters. Methods: Human circular esophageal strips were studied in organ baths and with microelectrodes. Responses following electrical stimulation (EFS) of enteric motor neurons (EMNs) or through nicotinic acetylcholine receptors (nAChRs) were compared in the esophageal body (EB), and in clasp and sling regions in the lower esophageal sphincter (LES). Results: In clasp LES strips: a) sodium nitroprusside (1nM-100μM), ADPβS (1-100μM), and VIP (1nM-1μM) caused a relaxation, b) L-NNA 1mM shifted the EFS-"on"-relaxation to an "off"-relaxation partly antagonized by 10µM MRS2179 or 10U/mL α-chymotrypsin; and c) nicotine-relaxation (100µM) was mainly antagonized by L-NNA, and only partly by MRS2179 or α-chymotrypsin. In sling LES fibers, EFS and nicotine-relaxation was abolished by L-NNA. In the EB, L-NNA blocked the latency period and MRS2179 reduced "off"-contraction. The amplitude of cholinergic contraction decreased from the EB to both LES sides. EFS induced a monophasic inhibitory junction potential (IJP) in clasp, sling and EB fibers abolished by L-NNA. Conclusions: Our study shows a regional specialization to stimulation of EMNs in the human esophagus with stronger inhibitory responses in clasp LES fibers and stronger cholinergic excitatory responses in the EB. Inhibitory responses are mainly triggered by nitrergic EMNs mediating the IJPs in the LES and EB, EFS-"on"-relaxation in clasp and sling LES sides and latency in the EB. We also found a minor role for purines (through P2Y(1) receptors) and VIP mediating part of non-nitrergic clasp LES relaxation.