PHARMACOLOGICAL PROPERTIES OF MECHANICAL RESPONSES OF THE RAT ESOPHAGEAL MUSCULARIS MUCOSAE TO VAGAL AND FIELD STIMULATION

Abstract

Electrical stimulation applied to vagal esophageal branches of the isolated curarized esophagus, or via field electrodes to the isolated tunica muscularis mucosae (TMM), increased longitudinal tension and intraluminal pressure in a frequency-dependent manner. Differences between cervical and distal TMM segments were noted in frequency-response relationships as well as in the pulse-width dependence of contractions to field stimulation. Vagally- and field-stimulated contractions were eliminated by tetrodotoxin or hyoscine, indicating their mediation by cholinergic neurons. The field-stimulated postganglionic responses were resistant to hexamethionium or (+)-tubocurarine and weakly inhibited by morphine. Vagally- and field-stimulated TMM contractions were mimicked by muscarinic agonists, augmented by acetylcholinesterase inhibitors and inhibited more effectively by .beta.- than by .alpha.1- or -.alpha.2-adrenoceptor agonists. 5-Hydroxytryptamine (5-HT) exerted excitatory and/or inhibitory effects: TMM in situ responded with a hexamethonium-resistant, ketanserin-sensitive transient increase in tension comparable to that produced by field stimulation. In the isolated TMM, moderate excitatory responses were limited to the distal portion with inhibition predominating in the remaining proximal portion. 5-HT-induced inhibitory effects on field-stimulated tension responses were paralleled by relaxant effects on muscarinic agonist-induced tonic contractile responses, both of which were resistant to 5-HT-receptor antagonists including ketanserin, LSD, methysergide or methergoline. Field stimulation at a low frequency and pulse durations > 1.0 ms produced a relaxation response in preparations exposed to tetrodotoxin or hyoscine, provided that active muscle tonus was present. The relaxation in response to field stimulation was insensitive to antagonists of 5-HT, catecholamines, histamine or indomethacin, suggesting a non-neurogenic origin. Histochemical examination of the isolated TMM preparation for cholinesterases revealed the presence of an extensive submucosal ganglionic plexus. It was concluded that intrinsic cholinergic neurons of the submucosal plexus form the final common pathway for extrinsic vagal and local (myenteric) projections to the TMM; the neural basis, if any, of non-cholinergic non-adrenergic inhibitory mechanisms remains to be established; and the TMM may assist in generating propulsive esophageal motility.