Evidence for the Pharmacological Similarity Between the Central Presynaptic Muscarinic Autoreceptor and Postsynaptic Muscarinic Receptors

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1982 Feb 1

PMID 7186824

Authors

D M Bowen

K L Marek

Affiliations

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Abstract

Twenty antagonist substances with varying potencies for central and peripheral postsynaptic muscarinic receptors have been examined for effects on the central presynaptic muscarinic autoreceptor. This has been monitored by measuring the stimulating effects of the substances on acetylcholine synthesis by rat neocortical tissue prisms. Dose-response curves for selected agents showed that maximal stimulation of synthesis was to 136-140% of the value without an antagonist. At a concentration of 1 microM, 17 of the substances caused a significant increase in synthesis, whilst at 0.01 microM significant stimulation occurred with only atropine, dexetimide, N-methyl-piperdin-4-yl (R)-2-cyclohexyl-2-hydroxyl-2-phenylacetate, quinuclidinyl benzilate (QNB) and scopolamine. Linear regression analysis between synthesis values obtained with the substances and published data for the effects on either cholinoceptor-agonist induced contraction of guinea-pig ileum or the binding of [3H]-QNB to rat forebrain membranes gave correlation coefficients of r = 0.84 (P less than 0.01), and r = 0.75 (P less than 0.02) respectively. The results provide no indication of a pharmacological difference between the central presynaptic muscarinic autoreceptor and central and peripheral postsynaptic muscarinic receptors.

References

Browning E, SCHULMAN M . (14C) acetylcholine synthesis by cortex slices of rat brain. J Neurochem. 1968; 15(12):1391-405. DOI: 10.1111/j.1471-4159.1968.tb05921.x. View

Golds P, Przyslo F, Strange P . The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol. 1980; 68(3):541-9. PMC: 2044199. DOI: 10.1111/j.1476-5381.1980.tb14570.x. View

Brimblecombe R, Green D, Inch T, Thompson P . The significance of differences in the potency of enantiomers of anti-acetylcholine drugs. J Pharm Pharmacol. 1971; 23(10):745-57. DOI: 10.1111/j.2042-7158.1971.tb08599.x. View

Lefresne P, Guyenet P, Glowinski J . Acetylcholine synthesis from (2- 14 C)pyruvate in rat striatal slices. J Neurochem. 1973; 20(4):1083-97. DOI: 10.1111/j.1471-4159.1973.tb00079.x. View

Szerb J, Somogyi G . Depression of acetylcholine release from cerebral cortical slices by cholinesterase inhibition and by oxotremorine. Nat New Biol. 1973; 241(108):121-2. DOI: 10.1038/newbio241121a0. View

Gibson G, Blass J . Inhibition of acetylcholine synthesis and of carbohydrate utilization by maple-syrup-urine disease metabolites. J Neurochem. 1976; 26(6):1073-8. DOI: 10.1111/j.1471-4159.1976.tb06988.x. View

Birdsall N, Hulme E . Biochemical studies on muscarinic acetylcholine receptors. J Neurochem. 1976; 27(1):7-16. DOI: 10.1111/j.1471-4159.1976.tb01536.x. View

Snyder S, Yamamura H . Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977; 34(2):236-9. DOI: 10.1001/archpsyc.1977.01770140126014. View

Hadhazy P, Szerb J . The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex. Brain Res. 1977; 123(2):311-22. DOI: 10.1016/0006-8993(77)90482-6. View

10.

Szerb J, Hadhazy P, Dudar J . Release of [3H]acetylcholine from rat hippocampal slices: effect of septal lesion and of graded concentrations of muscarnic agonists and antagonists. Brain Res. 1977; 128(2):285-91. DOI: 10.1016/0006-8993(77)90995-7. View

11.

Langer S . Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977; 60(4):481-97. PMC: 1667392. DOI: 10.1111/j.1476-5381.1977.tb07526.x. View

12.

Rospars J, Lefresne P, Beaujouan J, Glowinski J . Effect of external ACh and of atropine on 14C-ACh synthesis and release in rat cortical slices. Naunyn Schmiedebergs Arch Pharmacol. 1977; 300(2):153-61. DOI: 10.1007/BF00505046. View

13.

Lefresne P, Rospars J, Beaujouan J, Westfall T, Glowinski J . Effects of acetylcholine and atropine on the release of 14C-acetylcholine formed from U-14C-glucose in rat brain cortical and striatal prisms. Naunyn Schmiedebergs Arch Pharmacol. 1978; 303(3):279-85. DOI: 10.1007/BF00498055. View

14.

Delini-Stula A, Baumann P, BUCH O . Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and postsynaptic central noradrenergic receptor selectivity of alpha-adrenolytic drugs. Naunyn Schmiedebergs Arch Pharmacol. 1979; 307(2):115-22. DOI: 10.1007/BF00498452. View

15.

Garthwaite J, Woodhams P, Collins M, Balazs R . On the preparation of brain slices: morphology and cyclic nucleotides. Brain Res. 1979; 173(2):373-7. DOI: 10.1016/0006-8993(79)90641-3. View

16.

Yonehara N, Matsuda T, Saito K, Ishida H, Yoshida H . Effect of cyclic nucleotide derivatives on the release of ACh from cortical slices of the rat brain. Brain Res. 1980; 182(1):137-44. DOI: 10.1016/0006-8993(80)90836-7. View

17.

Sims N, Bowen D, Smith C, Flack R, Davison A, Snowden J . Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease. Lancet. 1980; 1(8164):333-6. DOI: 10.1016/s0140-6736(80)90884-3. View

18.

Richelson E . Temperature dependence of muscarinic acetylcholine receptor activation, desensitization, and resensitization. J Neurochem. 1980; 34(5):1288-95. DOI: 10.1111/j.1471-4159.1980.tb09973.x. View

19.

Kloog Y, Michaelson D, Sokolovsky M . Characterization of the presynaptic muscarinic receptor in synaptosomes of Torpedo electric organ by means of kinetic and equilibrium binding studies. Brain Res. 1980; 194(1):97-115. DOI: 10.1016/0006-8993(80)91321-9. View

20.

Garthwaite J, Woodhams P, Collins M, Balazs R . A morphological study of incubated slices of rat cerebellum in relation to postnatal age. Dev Neurosci. 1980; 3(2):90-9. DOI: 10.1159/000112381. View