Origin and modulation of circular smooth muscle layer contractions in the porcine esophagus

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.

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 1 mmol L(-1) , MRS2179 10 μmol L(-1) ) and excitatory neurotransmitters (atropine 1 μmol L(-1) ; SR140333 1 μmol L(-1) -NK(1) ra-, GR94800 1 μmol L(-1) -NK(2) ra-) and of ganglionic neurotransmitters (hexamethonium 100 μmol L(-1) , ondansetron 1 μmol L(-1) , NF279 10 μmol L(-1) ) were characterized.

Electrical field stimulation (EFS) induced a frequency-dependent off-contraction (16.8 ± 0.8 g) 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.

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 P2Y(1) 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.