Summary
Longitudinal muscle strips of the guinea-pig ileum were incubated with [3H]choline and the effects of muscarinic agonists on smooth muscle contraction and on spontaneous and electrically-evoked outflow of tritium were studied. Muscarine and pilocarpine concentration-dependently increased both muscle contraction and spontaneous outflow of [3H]ACh, and inhibited the electrically-evoked outflow of [3H]ACh. The increase in spontaneous outflow was prevented by tetrodotoxin and scopolamine, but not by hexamethonium. Oxotremorine (1–100 μM) did not increase the spontaneous outflow of tritium.
Pirenzepine in concentrations of 10 and 100 nM hardly affected the muscle contractions induced by pilocarpine, but significantly antagonized the pilocarpine-evoked increases in [3H]ACh outflow. Likewise, pirenzepine (100 nM) antagonized more effectively the enhancement by muscarine of spontaneous outflow than the inhibitory effect of muscarine on the electrically-evoked release of [3H]ACh. Scopolamine (1 and 10 nM) antagonized to a similar extent the effects of pilocarpine on spontaneous outflow of [3H]ACh and on muscle contraction.
The results suggest that the cholinergic nerves of the myenteric plexus are endowed with excitatory (ganglionic) and inhibitory (prejunctional) muscarine receptors which modulate the release of ACh and which differ in their affinities to pirenzepine.
Similar content being viewed by others
References
Birdsall NJM, Hulme EC (1983) Muscarinic receptor subclasses. Trends Pharmacol Sci 4:459–463
Brown DA, Forward A, Marsh S (1980) Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br J Pharmacol 71:362–364
Buckley N, Burnstock G (1984) Autoradiographic localization of peripheral muscarinic receptors. Trends Pharmacol Sci (Suppl January 1984) 55–59
Kilbinger H, Wessler I (1980) Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 314:259–266
Kilbinger H (1984a) Presynaptic muscarine receptors modulating acetylcholine release. Trends Pharmacol Sci 5:103–105
Kilbinger H (1984 b) Facilitation and inhibition by muscarinic agonists of acetylcholine release from guinea-pig myenteric neurones: mediation through different types of neuronal muscarinic receptors. Trends Pharmacol Sci (Suppl January 1984) 49–52
Kilbinger H, Halim S, Lambrecht G, Weiler W, Wessler I (1984) Comparison of affinities of muscarinic antagonists to pre- and postjunctional receptors in the guinea-pig ileum. Eur J Pharmacol 103:313–320
Morita K, North RA, Tokimasa T (1982 a) Muscarinic agonists inactivate potassium conductance of guinea-pig myenteric neurones. J Physiol 333:125–139
Morita K, North RA, Tokimasa T (1982 b) Muscarinic presynaptic inhibition of synaptic transmission in myenteric plexus of guinea-pig ileum. J Physiol 333:141–149
Ochillo RF, Tsai CS, Tsai MH (1981) Mechanism of action of muscarine on the longitudinal muscle of the guinea-pig isolated ileum. Br J Pharmacol 72:225–232
Rang HP (1966) The kinetics of action of acetylcholine antagonists in smooth muscle. Proc Roy Soc London B 164:488–510
Von Schwarzenfeld I (1979) Origin of transmitters released by electrical stimulation from a small metabolically very active vesicular pool of cholinergic synapses in guinea-pig cerebral cortex. Neurosci 4:477–493
Watson M, Vickroy TW, Roeske WR, Yamamura HI (1984) Subclassification of muscarinic receptors based upon the selective antagonist pirenzepine. Trends Pharmacol Sci (Suppl January 1984) 9–11
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kilbinger, H., Nafziger, M. Two types of neuronal muscarine receptors modulating acetylcholine release from guinea-pig myenteric plexus. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 304–309 (1985). https://doi.org/10.1007/BF00515558
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00515558