Abstract
Background The origin and modulation mechanisms controlling timing and amplitude of esophageal body peristalsis are not fully understood. We aimed to characterize the neurotransmitters involved in the origin and modulation of circular smooth muscle esophageal body (EB) contractions. Methods Responses of porcine EB strips to electrical stimulation of motor neurons (MNs) were assessed in organ baths and with microelectrodes. The effect of antagonists of inhibitory (L-NAME 1mmolL-1, MRS2179 10μmolL-1) and excitatory neurotransmitters (atropine 1μmolL-1; SR140333 1μmolL-1-NK1ra-, GR94800 1μmolL-1-NK2ra-) and of ganglionic neurotransmitters (hexamethonium 100μmolL-1, ondansetron 1μmolL-1, NF279 10μmolL-1) were characterized. Key Results Electrical field stimulation (EFS) induced a frequency-dependent off-contraction (16.8±0.8g) following a latency period. Latency was significantly reduced by L-NAME (-66.1±4.1%) and MRS2179 (-25.9±5.6%), and strongly increased by atropine (+36.8±5.8%). Amplitude was reduced by L-NAME (-69.9±10.4%), MRS2179 (-34.1±6.0%), atropine (-42.3±4.7%), hexamethonium (-18.9±3.3%), NF279 (-20.7±3.5%), ondansetron (-16.3±3.2%), GR94800 (-28.0±4.8%) SR140333 (-20.9±7.1%), and α-chymotrypsin (-31.3±7.0%). The EFS induced a monophasic nitrergic inhibitory junction potential. Conclusions & Inferences Our results suggest that timing (latency) and amplitude of esophageal contractions are determined by a balance of complex interactions between excitatory and inhibitory MNs. Latency depends on the activation of inhibitory MNs releasing NO and a minor purinergic contribution through P2Y1 receptors, and excitatory MNs releasing ACh. Amplitude depends on a major contribution of excitatory MNs releasing ACh and tachykinins, and also on inhibitory MNs releasing NO, ATP or related purines, and peptidergic neurotransmitters acting as strong modulators of the excitatory neuroeffector transmission. © 2012 Blackwell Publishing Ltd.
Original language | English |
---|---|
Journal | Neurogastroenterology and Motility |
Volume | 24 |
Issue number | 8 |
DOIs | |
Publication status | Published - 1 Aug 2012 |
Keywords
- Circular esophageal smooth muscle
- Esophageal peristalsis
- Esophageal smooth muscle contraction
- Excitatory and inhibitory motor neurons
- Inhibitory junction potential
- Ligand-gated ion channels
- Modulation of esophageal peristalsis
- Neuromuscular transmission
- Porcine esophagus