Selective stimulation of intrinsic excitatory and inhibitory motor pathways in porcine lower oesophageal sphincter.

The mechanisms of stimulation of inhibitory and excitatory motor neurons (MNs) in the lower oesophageal sphincter (LOS) are not fully understood. The aim of this study was to assess the effect of selective stimulation of inhibitory and excitatory MNs in porcine LOS through nicotinic acetylcholine receptors (nAChRs), 5-HT(3) and P2X receptors. Circular LOS strips from adult pigs were studied in organ baths. We compared the effects of stimulation of MNs by electrical field stimulation (26 V, 0.3-20 Hz); nicotine (1-300 micromol L(-1)); 5-HT and 2-Me-5-HT (1 nmol(-1)-30 micromol L(-1)); and alpha,beta-methylene ATP (alpha,beta-meATP 1-100 micromol L(-1)); in standard Krebs solution; a non-adrenergic non-nitrergic non-purinergic (NANNNP) solution; and a non-adrenergic non-cholinergic (NANC) solution. Electrical stimulation of inhibitory MNs caused an intense LOS relaxation (-78.94 +/- 4.50% of LOS tone); and of excitatory MNs, a strong contraction (17.89 +/- 1.96 g). Nicotine 100 micromol L(-1) relaxed LOS (-84.67 +/- 3.98%) in standard Krebs solution, an effect reduced by Tetrodotoxin (TTX) 1 micromol L(-1). Nicotine induced a weak TTX-sensitive contraction (1.64 +/- 0.4 g) in NANNNP solution. 5-HT 10 micromol L(-1) and 2-Me-5-HT 30 micromol L(-1) contracted LOS in standard, NANC and NANNNP conditions, maximal responses (7.30 +/- 1.52 g, 3.50 +/- 0.18 g respectively) being reduced by TTX. alpha,beta-meATP 100 micromol L(-1) caused a LOS relaxation (-17.45 +/- 6.62%) unaffected by TTX in NANC solution, and a contraction (6.7 +/- 0.85 g) antagonized by TTX in NANNNP solution. Our results suggest selective mechanisms for stimulation of intrinsic excitatory and inhibitory motor pathways in porcine LOS. Inhibitory MNs are strongly stimulated by nAChRs and do not respond to stimulation of 5-HT(3) and P2X receptors. By contrast, excitatory MNs are stimulated through 5-HT(3) and P2X receptors, stimulation through nACRs being difficult and causing a weak response.