Noncholinergic nonadrenergic inhibitory innervation of the canine pylorus

Abstract

Vagal nerve stimulation in atropine-treated dogs leads to an inhibitory motor response at the pylorus. The roles played by the cholinergic and the adrenergic nervous systems in this response were investigated in pentobarbital-anesthetized dogs. Force transducers were sutured to the gastric antrum, pylorus, and duodenum. Electrical vagal stimulation of the distal cut ends of the thoracic vagi was performed for 1-min periods. Minute motility indices were obtained for prestimulatory, stimulatory, and poststimulatory motor activity before and after each drug administration. Atropine sulfate (0.1–1.0 mg/kg i.v.) was administered to all animals. After atropine administration, 12 dogs received hexamethonium bromide as a bolus intravenous injection (30 mg/kg) and seven dogs received hexamethonium by infusion (60 mg/kg/hr i.v.). A second group of six dogs received the infusion of hexamethonium first, followed by atropine injection. A third group of 11 dogs received atropine followed by phenoxybenzamine, phentolamine, and propranolol (each at 4 mg/kg i.v.). Guanethidine sulfate (4 mg/kg i.v.) was administered either after the adrenergic receptor antagonists and atropine (eight dogs) or after atropine alone (four dogs). Following atropine injection, spontaneous contractile activity was observed only in the pylorus. Vagal stimulation produced significant inhibition of this activity and, in a majority of the animals, a concomitant relaxation of the pyloric tone. Hexamethonium infusion, but not bolus injection, blocked the pyloric inhibition, relaxation response. Vagal stimulation during the infusion of hexamethonium without atropine produced an excitatory response in the antrum and pylorus. None of the drugs affecting the adrenergic nervous system prevented the vagally mediated inhibitory response. The inhibition, relaxation response of the canine pylorus to vagal stimulation is noncholinergic and nonadrenergic and is mediated through nicotinic and possibly muscarinic ganglionic receptors. The nervous pathways for the vagally mediated excitatory pyloric responses utilize both nicotinic and muscarinic synaptic transmission. The canine pylorus appears to be a physiologically unique zone.