Facilitation, and muscarinic and alpha-adrenergic inhibition of the secretion of 3H-acetylcholine and 3H-noradrenaline from guinea-pig ileum myenteric nerve terminals

Abstract

The transmitter stores of cholinergic and noradrenergic neurons in guinea-pig ileum myenteric plexus were labelled by preincubation with 3H-choline or 3H-noradrenaline (3H-NA), respectively. Secretion of transmitter was evoked by electrical field stimulation. In the presence (but not in the absence) of eserine (10 microM) the secretion of 3H-acetylcholine (3H-ACh) per shock increased with the frequency of stimulation. Half maximal secretion was obtained at 0.7 Hz (apparent Km Freq). Variation in number of shocks per train did not influence the secretory response per shock (at 6 Hz). The secretion of 3H-NA per shock also increased with the frequency of stimulation (Km Freq = 1.5 Hz). Comparison of the inhibitory effects of oxotremorine and of exogenous NA, on the secretory responses to stimulation at frequencies close to Km Freq, showed that the secretory mechanisms of both neurons are 13-17-fold more sensitive to the inhibitory effect of their 'own', than to that of 'foreign', agonist. In both types of neuron the inhibitory effects of oxotremorine and of NA were competitively antagonized by atropine and by yohimbine, respectively. Dissociation constants for the respective antagonist were essentially the same, irrespectively of the type of neuron, indicating that the properties of 'presynaptic' muscarinic or alpha-receptors are independent of whether they occur on cholinergic or on noradrenergic terminals.