6533b82dfe1ef96bd1291ef2

RESEARCH PRODUCT

Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum

subject

description

The effects of several muscarinic agonists on smooth muscle (postsynaptic effect) and on acetylcholine release (presynaptic effect) were compared in the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum. 1. For release experiments the acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation in the absence of a cholinesterase inhibitor caused an outflow of tritium that reflected release of 3H-acetylcholine. The agonists oxotremorine, arecaidinepropargylester, methylfurmethide, muscarine, carbachol, arecoline and pilocarpine inhibited the stimulation-induced outflow in a concentration-dependent manner. At the highest concentrations used, the drugs depressed the evoked outflow by 83–96%. Scopolamine (10nM) antagonized the inhibitory effects of all agonists which suggests that the reduction of outflow was mediated by muscarine receptors. 2. Oxotremorine (100nM) depressed the twitch response to field stimulation at 0.1 Hz. The inhibitory effect was overcome by scopolamine (3nM). The twitch-inhibitory effect of oxotremorine is thought to result from stimulation of presynaptically located muscarine receptors. 3. All agonists contracted the longitudinal muscle in a concentration-dependent fashion. The rank orders of potencies for pre- and postsynaptic effects were dissimilar. Furthermore, the potency ratios (measured as EC 50 presynaptic: EC 50 postsynaptic) were not constant but varied from 0.37 (oxotremorine) to 2.9 (acetylcholine). The results suggest that pre-and postsynaptic muscarine receptors in the longitudinal muscle-myenteric plexus preparation differ slightly in their pharmacological properties.