Vasoactive intestinal polypeptide and non‐adrenergic, non‐cholinergic inhibition in lower oesophageal sphincter of opossum

Abstract

1 Field stimulation or vasoactive intestinal polypeptide (VIP) relaxed lower oesophageal sphincter (LOS) from North American opossum. Pretreatment with carbachol in Cl-ion-containing or Cl-ionfree Krebs solution or with 10 -M 9-aminoacridine abolished or markedly reduced relaxation due to VIP applied exogenously but not that elicited by field stimulation of non-adrenergic, noncholinergic nerves. 2 Inhibitory junction potentials (7.5 + 1.2 mV, n = 5) could be recorded in LOS strips with the sucrose gap technique. They lacked significant after-depolarizations but were accompanied by decreased membrane resistance (61 + 6%, n = 3). In these strips, VIP (10-6M) produced small hyperpolarizations (2.1 + 1.1 mV, n = 5) sometimes followed by membrane potential oscillations but no change in conductance. 3 Removal of external chloride depolarized the membranes (7.6 + 1.7 mV) but did not prevent the hyperpolarization to VIP or the occurrence of inhibitory junction potentials. Restoration of external chloride repolarized the cells. It appears that an appreciable chloride conductance may be present in sphincter muscle cells and this may cause them to be more depolarized than nonsphincter muscle. 4 We conclude that it is very unlikely that VIP is the inhibitory NANC neurotransmitter since it does not mimic the inhibitory junction potential.

Mechanical activity of frog esophagus muscle in response to electrical stimulation of intramural nerves

“…These results suggest that the relaxation response is produced by NANC inhibitory nerve excitation. NANC inhibitory nerves have been reported to be present in the guinea-pig caecum (Burnstock et al, 1966), the dog stomach (Ohga et al, 1970), the opossum esophageal sphincter (Daniel et al, 1989), the human uterus (Jones et al, 1997) and the monkey uterus (Kuenzli et al, 1998). The present experiments have demonstrated that functional NANC inhibitory nerves are distributed in the frog esophagus.…”

“…Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are known as the transmitter substances released from NANC inhibitory nerves (Daniel et al, 1989: Desai et al, 1991: Bayguinov et al, 1999. Further study is required to elucidate the transmitter substances released by NANC excitatory and inhibitory nerves in the smooth muscle of the frog esophagus.…”

Nitrinergic and peptidergic innervation of the human oesophagus.

“…1 Functional studies have suggested that the peptides, vasoactive intestinal polypeptide (VIP), and calcitonin gene related peptide (CGRP) may be candidate NANC inhibitory neurotransmitters in the oesophagus. [2][3][4] Morphological studies in the human oesophagus and in experimental animals show abundant VIP and CGRP in the myenteric plexus, and VIP and CGRP positive fibres in the muscle layers. [5][6][7][8][9][10][11][12] It has now been shown that nitric oxide or a related product of the L-arginine-nitric oxidesynthase pathway may participate in the oesophageal smooth muscle relaxation, latencies of oesophageal contraction, and oesophageal off contraction in the opossum as well as in humans.…”

Electrophysiological Properties of Inhibitory Junction Potential in Murine Lower Oesophageal Sphincter.

“…Clarification of the underlying mechanisms of the generation of IJP leads to the identification not only of the transmitter(s) but also of the channel(s) involved in these hyperpolarising responses. IJP in LOS are observed in several experimental animals, for example dog (Allescher et al, 1988), opossum (Daniel et al, 1989;Conklin et al, 1993), guineapig (Imaeda et al, 1998;Yuan et al, 1998) and mouse (Ward et al, 1998). In the guinea-pig LOS, nitric oxide (NO) and adenosine triphospahte (ATP) have been proposed as inhibitory neurotransmitters and small conductance Ca 2+ -activated K + (SKCa) channels played an important role in eliciting IJP (Imaeda et al, 1998).…”