Nature of the vagal inhibitory innervation to the lower esophageal sphincter.

Abstract

A B S T R A C T The purpose of the present study was to investigate the nature of the vagal inhibitory innervation to the lower esophageal sphincter in the anesthetized opossum. Sphincter relaxation with electrical stimulation of the vagus was not antagonized by atropine, propranolol, phentolamine, or by catecholamine depletion with reserpine. A combination of atropine and propranolol was also ineffective, suggesting that the vagal inhibitory influences may be mediated by the noncholinergic, nonadrenergic neurons. To determine whether a synaptic link with nicotinic transmission was present, we investigated the effect of hexamethonium on vagal-stimulated lower esophageal sphincter relaxation. Hexamethonium in doses that completely antagonized the sphincter relaxation in response to a ganglionic stimulant, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), did not block the sphincter relaxation in response to vagal stimulation at 10 pulses per second, an optimal frequency of stimulation. A combination of hexamethonium and catecholamine depletion was also ineffective, but hexamethonium plus atropine markedly antagonized sphincter relaxation (P < 0.001). Moreover, 4-(m-chlorophenyl carbamoyloxy) -2-butyltrimethylammonium chloride (McN-A-343), a muscarinic ganglionic stimulant, also caused relaxation of the lower esophageal sphincter. We suggest from these results that: (a) the vagal inhibitory pathway to the sphincter consists of preganglionic fibers which synapse with postganglionic neurons: (b) the synaptic transmission is predominantly cholinergic and utilizes nicotinic as well as muscarinic receptors on the postganglionic neuron, and; (c) postganglionic neurons exert their influence on the sphincter by an unidentified inhibitory transmitter that is neither adrenergic nor cholinergic.

Characterization of nerve-induced relaxation of gastrointestinal sphincteric smooth muscle in a South American opossum (Didelphis albiventris)

“…Since this opossum species is not readily available to us, in the present study we characterized in vitro the nerve-induced responses of the circular smooth muscle from gastrointestinal sphincters of the closely related opossum species Didelphis albiventris, readily available in SA. Our results show that, as described for isolated strips of circular smooth muscle from the esophagogastric and ileocecal junctions of other species including humans (14)(15)(16)(17)(18)(19)(20)(21), the strips from these regions obtained from the SA opossum developed spontaneous tension which was not influenced by atropine or adrenergic blockers. The fact that TTX raised the tension in the ileocolonic junction but not in the lower esophageal sphincter or pyloric strips indicates the presence of an intrinsic tonic inhibitory innervation in this region.…”

“…The fact that atropine reduced the EFS-induced contraction and enhanced the magnitude of the relaxant responses in both strips while guanethidine and adrenergic blockers failed to affect the relaxations indicates that the latter are caused by the activation of NANC nerves. Inhibitory NANC nerves of the circular smooth muscle from the lower esophageal sphincter and ileocolonic junction have been described in several species including NA opossums, cats, dogs and humans (20)(21)(22)(23). The fact that nicotine also caused relaxations of the lower esophageal sphincter and ileocolonic junction in a hexamethonium-and TTX-sensitive manner suggests that the intrinsic NANC neurons of these regions from the SA opossum are activated by nicotinic receptor stimulation.…”

Role of vasoactive intestinal polypeptide in the internal anal sphincter relaxation of the opossum.

“…Such noncholinergic, nonadrenergic nerves play a significant role in the relaxation of a variety of smooth muscle tissues (6, 1. Abbreviations used in this paper: D50, dose producing 50% of the maximal response; EFS, electrical field stimulation; GRF analogue, (N-Ac-Tyr',D-Phe2)-GRF 7). However, the exact nature ofthe inhibitory neurotransmitter responsible for the relaxation of these smooth muscle tissues and IAS relaxation is not known.…”

Sympathetic Control of Lower Esophageal Sphincter Function in the Cat

“…However, when the vagi were cut in the neck, LES pressure was not reduced (10). Furthermore, direct vagal stimulation led to a nonadrenergic, noncholinergic (puringergic) relaxation in LES tone (3,11). The absence of excitatory cholinergic innervation to the LES within the vagus has led to certain doubts that the LES received any direct excitatory cholinergic innervation (3).…”

“…The vagi serve a major role in the initiation of LES relaxation during swallowing (1,2). Excitatory cholinergic pathways in the vagi have been difficult to demonstrate in the opossum, but may be present in the cat (3,4). Our understanding of the influence of vagal function on the LES had developedl through studies designed to inhibit or stimulate the vagi directly (1,2).…”