Modulation by Scopolamine, Acetylcholine and Choline of the Evoked Release of Acetylcholine from the Guinea Pig Myenteric Plexus: Evidence for a Muscarinic Feedback Inhibition of Acetylcholine Secretion

Abstract

There is evidence that the release of acetylcholine (ACh) from the guinea pig myenteric plexus is controlled via presynaptic muscarine receptors. Muscarinic antagonists such as atropine enhance the release evoked by either electrical field stimulation, by nicotinic drugs or by high K+ concentrations (4,7,10). On the other hand, the muscarinic agonist oxotremorine inhibits the evoked release of ACh (7). A comparable feedback inhibition has been described for the release of ACh from central cholinergic nerves (for review, see Ref. 12). However, it has so far not been shown whether the physiological transmitter itself is able to depress the release of neuronal ACh. We have, therefore, studied the effects of extracellular ACh on the release of labelled neuronal ACh from the longitudinal muscle-myenteric plexus preparation of the guinea pig. In addition, the effects of scopolamine and choline (Ch) on the evoked outflow of labelled ACh in the absence of a Cholinesterase inhibitor were investigated. The measurement of ACh release from the myenteric plexus without Cholinesterase inhibition was based on the method described by Szerb (11); incubation of the myenteric plexus preparation with [3H]-Ch leads to the formation of [3H]-ACh in the tissue. Electrical field stimulation causes an outflow of [3H]-Ch which originates from the release of [3H]-ACh that is hydrolyzed by cholinesterase.