Pharmacological properties of mechanical responses of the rat oesophageal muscularis mucosae to vagal and field stimulation
Electrical stimulation applied to vagal oesophageal branches of the isolated curarized oesophagus, 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 neurones. The field-stimulated postganglionic responses were resistant to hexamethonium 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, lysergic acid diethylamide (LSD), methysergide or methergoline. Field stimulation at a low frequency and pulse durations greater than 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 is concluded that: (i) intrinsic cholinergic neurones of the submucosal plexus form the final common pathway for extrinsic vagal and local (myenteric) projections to the TMM; (ii) the neural basis, if any, of non-cholinergic non-adrenergic inhibitory mechanisms remains to be established; (iii) the TMM may assist in generating propulsive oesophageal motility.