6533b862fe1ef96bd12c6bcd

RESEARCH PRODUCT

Control of Acetylcholine Release and of Intestinal Motility by Subtypes of Muscarine Receptors

subject

description

Two types of neuronal muscarine receptors have been investigated in the myenteric plexus preparation of the guinea-pig small intestine: 1. Presynaptic receptors activation of which inhibits the depolarization-evoked release of acetylcholine. Pirenzepine and dicyclomine have low affinities to the release-inhibitory receptors (pA2 values 6.9 and 7.6) which suggests that the presynaptic receptors (similar to the smooth muscle receptors) belong to the M2 subtype. The inhibition of the electrically-evoked acetylcholine release by muscarine (0.01 - 1 μmol/1) was not affected by forskolin (1μmol/l). This indicates that cyclic AMP is not crucially involved in the muscarinic inhibition of acetylcholine release. 2. Somatodendritic receptors whose activation causes an increase in spontaneous acetylcholine release. These receptors have a high affinity to pirenzepine pA2 8.5)and dicyclomine (pA2 9.3), and thus belong to the M1 subtype. M1 receptors are probably involved in the regulation of intestinal motility. Blockade by low concentrations (<1 nmol/1) of either pirenzepine or dicyclomine causes an increase in intestinal peristalsis. This increase is antagonized by bicuculline (10 nmol/1). The results suggest that the activation of ganglionic M1 receptors by endogenous acetylcholine leads to an increased release of γ-aminobutyric acid which, in turn, causes inhibition of intestinal motility.