The role of the intramural cholinergic innervation in the acid response of the parietal cell to gastrin derivatives.

Abstract

The action of a number of nerve-blocking agents on gastric secretion in fundic pouches in dogs has been investigated. Histamine has been used as a direct acid stimulant, and was compared with gastrin and derivatives whose action may involve local nerves. In most cases, the inhibitor agent has been applied to an established plateau of secretion but in some series the local anesthetic lidocaine (xylocaine) benzyl chloride (LBC) has been allowed to act for [Formula: see text] h before stimulation was commenced.In Heidenhain pouches, atropine (5–20 μg/kg intravenously (i.v.)) produced a mean inhibition of submaximal pentagastrin and gastrin plateaus of –88%. Histamine plateaus were inhibited only –21%. Hexamethonium (1 mg/kg i.v.) was without effect on the pentagastrin response. This means that only the terminal element of the cholinergic pathway can be involved in gastrin stimulation of the parietal cell.Blockage of this terminal link was demonstrated in Pavlov pouches under insulin stimulation by pretreatment with LBC, the mean inhibition being –95%. Pepsin secretion was also abolished. LBC was without effect on established histamine plateaus in Heidenhain pouches and the same result was observed with stimulation by gastrin and its derivatives. This last result, implying no nervous involvement in the gastrin effect, led to recognition of a difference in design in the insulin experiments where LBC was applied before acid secretion.Experiments with LBC on established insulin responses gave an inhibition of only –44%. Thus a series of pentagastrin experiments with pretreatment were carried out but the mean inhibition was only –15%, which is not significant. This is directly comparable with the mean inhibition in the LBC pretreatment insulin series of –95%.To exclude nonspecific effects of LBC, sodium net flux studies have been carried out. There was a small increase in positive Na+ net flux in the vagal stimulation in which the acid response is virtually abolished. However, in the pentagastrin experiments with LBC pretreatment, larger positive net sodium fluxes occurred though acid secretion was not significantly reduced. It is therefore considered that the powerful inhibition in the vagal stimulation experiments is not related to nonspecific effects.It is concluded that the acid secretory response of the parietal cell to gastrin derivatives does not involve excitation of intramural cholinergic nerve elements as now seems likely for their motor effects. However, the response of the parietal cell to gastrin acting directly may be potentiated by quantal acetylcholine release from resting fibers, and until this possibility is excluded the blocking effects of atropine cannot be regarded as nonspecific.