Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release

E. S. Vizi, O. Kobayashi, A. Töröcsik, M. Kinjo, H. Nagashima, N. Manabe, P. L. Goldiner, P. E. Potter, F. F. Foldes

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Abstract

In order to extend the characterization of muscarinic receptors at presynaptic sites their inhibitory effect on the stimulation-evoked release of [3H]noradrenaline and [3H]acetylcholine from different axon terminals was studied and the dissociation constants and potencies of different antagonists were estimated, in guinea-pig and rat. While oxotremorine reduced the release of [3H]acetylcholine and [3H]noradrenaline in a concentration-dependent manner from different release sites (Auerbach plexus, noradrenergic neurons in the right atrium, cerebral cortex), McN-A 343, an M1 receptor agonist, enhanced their release evoked by field stimulation. When the inhibitory effect of oxotremorine on transmitter release was studied, pancuronium, pirenzepine and atropine were competitive antagonists of presynaptic muscarinic receptors located on the noradrenergic axon terminals of the atrium. While atropine and pirenzepine inhibited the muscarinic receptors of cholinergic axon terminals in the Auerbach plexus, pancuronium and gallamine had a very low affinity. Significant differences were found in the affinity constants of antagonists for muscarinic receptors located in the cholinergic axon terminals of Auerbach plexus and cerebral cortex, and noradrenergic axon terminals of the atrium. While atropine and pirenzepine exerted similar effects on these presynaptic sites, pancuronium, gallamine and (1 1-(2-((diethylamino)-methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6(1-pyrido(2,3-b)(1,4)benzodiazepin-6-on) were much more effective on muscarinic receptors controlling acetylcholine release from the cerebral cortex and noradrenaline release from the heart. There was more than 100-fold (2.0 pA2 units) difference in affinities of these antagonists. Therefore, existence of three different subtypes of presynaptic muscarinic receptors is suggested: M1, which mediates increase of acetylcholine and noradrenaline release; M2, which mediates inhibition of acetylcholine release from the Auerbach plexus; and M3, which mediates inhibition of acetylcholine release from cerebral cortex and noradrenaline release from sympathetic axon terminals of the right atrium.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalNeuroscience
Volume31
Issue number1
DOIs
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Neuroscience(all)

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    Vizi, E. S., Kobayashi, O., Töröcsik, A., Kinjo, M., Nagashima, H., Manabe, N., Goldiner, P. L., Potter, P. E., & Foldes, F. F. (1989). Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release. Neuroscience, 31(1), 259-267. https://doi.org/10.1016/0306-4522(89)90048-1