Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Apr;93(4):855–862. doi: 10.1111/j.1476-5381.1988.tb11472.x

A quantitative study of the effects of some muscarinic antagonists on the guinea-pig olfactory cortex slice.

S H Williams 1, A Constanti 1
PMCID: PMC1853873  PMID: 3390654

Abstract

1. Muscarinic depression of the electrically-evoked surface-negative field potential (N-wave) was measured in guinea-pig olfactory cortex slices maintained in vitro. 2. The effects of three muscarinic receptor antagonists, pirenzepine, atropine and gallamine on this muscarinic response were analysed in detail. 3. Pirenzepine was a potent competitive antagonist of carbachol (CCh)-evoked responses. Schild plot analysis yielded a pA2 value of 7.9 (Schild slope constrained to unity). A similar analysis for atropine versus CCh responses gave a pA2 of 8.9. 4. Combination experiments using pirenzepine and atropine produced dose-ratio shifts close to those expected for two antagonists competing for a similar receptor site. 5. Gallamine was only a weak antagonist of responses to CCh. 6. Oxotremorine behaved as a competitive antagonist at this muscarinic receptor (pA2 = 6.1). 7. It is concluded that the presynaptic muscarinic receptor mediating depression of the N-wave in the olfactory cortex slice is of the M1-subtype.

Full text

PDF
855

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown D. A., Fatherazi S., Garthwaite J., White R. D. Muscarinic receptors in rat sympathetic ganglia. Br J Pharmacol. 1980 Dec;70(4):577–592. doi: 10.1111/j.1476-5381.1980.tb09777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown D. A., Forward A., Marsh S. Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br J Pharmacol. 1980;71(2):362–364. doi: 10.1111/j.1476-5381.1980.tb10948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Choo L. K., Mitchelson F., Vong Y. M. The interaction of McN-A-343 with pirenzepine and other selective muscarine receptor antagonists at a prejunctional muscarine receptor. Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):430–438. doi: 10.1007/BF00692912. [DOI] [PubMed] [Google Scholar]
  4. Clark A. L., Mitchelson F. The inhibitory effect of gallamine on muscarinic receptors. Br J Pharmacol. 1976 Nov;58(3):323–331. doi: 10.1111/j.1476-5381.1976.tb07708.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Constanti A., Sim J. A. Calcium-dependent potassium conductance in guinea-pig olfactory cortex neurones in vitro. J Physiol. 1987 Jun;387:173–194. doi: 10.1113/jphysiol.1987.sp016569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Constanti A., Sim J. A. Muscarinic receptors mediating suppression of the M-current in guinea-pig olfactory cortex neurones may be of the M2-subtype. Br J Pharmacol. 1987 Jan;90(1):3–5. doi: 10.1111/j.1476-5381.1987.tb16818.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cortés R., Palacios J. M. Muscarinic cholinergic receptor subtypes in the rat brain. I. Quantitative autoradiographic studies. Brain Res. 1986 Jan 8;362(2):227–238. doi: 10.1016/0006-8993(86)90448-8. [DOI] [PubMed] [Google Scholar]
  8. Egan T. M., North R. A. Acetylcholine acts on m2-muscarinic receptors to excite rat locus coeruleus neurones. Br J Pharmacol. 1985 Aug;85(4):733–735. doi: 10.1111/j.1476-5381.1985.tb11070.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Egan T. M., North R. A. Acetylcholine hyperpolarizes central neurones by acting on an M2 muscarinic receptor. 1986 Jan 30-Feb 5Nature. 319(6052):405–407. doi: 10.1038/319405a0. [DOI] [PubMed] [Google Scholar]
  10. Hammer R., Berrie C. P., Birdsall N. J., Burgen A. S., Hulme E. C. Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature. 1980 Jan 3;283(5742):90–92. doi: 10.1038/283090a0. [DOI] [PubMed] [Google Scholar]
  11. Hammer R., Giachetti A. Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization. Life Sci. 1982 Dec 27;31(26):2991–2998. doi: 10.1016/0024-3205(82)90066-2. [DOI] [PubMed] [Google Scholar]
  12. Kubo T., Fukuda K., Mikami A., Maeda A., Takahashi H., Mishina M., Haga T., Haga K., Ichiyama A., Kangawa K. Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature. 1986 Oct 2;323(6087):411–416. doi: 10.1038/323411a0. [DOI] [PubMed] [Google Scholar]
  13. Lazareno S., Kendall D. A., Nahorski S. R. Pirenzepine indicates heterogeneity of muscarinic receptors linked to cerebral inositol phospholipid metabolism. Neuropharmacology. 1985 Jun;24(6):593–595. doi: 10.1016/0028-3908(85)90071-1. [DOI] [PubMed] [Google Scholar]
  14. Mash D. C., Potter L. T. Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain. Neuroscience. 1986 Oct;19(2):551–564. doi: 10.1016/0306-4522(86)90280-0. [DOI] [PubMed] [Google Scholar]
  15. North R. A., Slack B. E., Surprenant A. Muscarinic M1 and M2 receptors mediate depolarization and presynaptic inhibition in guinea-pig enteric nervous system. J Physiol. 1985 Nov;368:435–452. doi: 10.1113/jphysiol.1985.sp015867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Raiteri M., Leardi R., Marchi M. Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain. J Pharmacol Exp Ther. 1984 Jan;228(1):209–214. [PubMed] [Google Scholar]
  17. Ringdahl B. Determination of dissociation constants and relative efficacies of oxotremorine analogs at muscarinic receptors in the guinea-pig ileum by pharmacological procedures. J Pharmacol Exp Ther. 1984 Apr;229(1):199–206. [PubMed] [Google Scholar]
  18. Ringdahl B., Jenden D. J. Affinity, efficacy, and stereoselectivity of oxotremorine analogues for muscarinic receptors in the isolated guinea pig ileum. Mol Pharmacol. 1983 Jan;23(1):17–25. [PubMed] [Google Scholar]
  19. STEPHENSON R. P. A modification of receptor theory. Br J Pharmacol Chemother. 1956 Dec;11(4):379–393. doi: 10.1111/j.1476-5381.1956.tb00006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith K. J., Schauf C. L. Gallamine triethiodide (flaxedil): tetraethylammonium- and pancuronium-like effects in myelinated nerve fibers. Science. 1981 Jun 5;212(4499):1170–1172. doi: 10.1126/science.7233212. [DOI] [PubMed] [Google Scholar]
  21. Watson M., Yamamura H. I., Roeske W. R. A unique regulatory profile and regional distribution of [3H]pirenzepine binding in the rat provide evidence for distinct M1 and M2 muscarinic receptor subtypes. Life Sci. 1983 Jun 27;32(26):3001–3011. doi: 10.1016/0024-3205(83)90652-5. [DOI] [PubMed] [Google Scholar]
  22. Williams S. H., Constanti A., Brown D. A. Muscarinic depression of evoked surface-negative field potentials recorded from guinea-pig olfactory cortex in vitro. Neurosci Lett. 1985 May 23;56(3):301–306. doi: 10.1016/0304-3940(85)90259-9. [DOI] [PubMed] [Google Scholar]
  23. Williams S. H., Constanti A. Quantitative effects of some muscarinic agonists on evoked surface-negative field potentials recorded from the guinea-pig olfactory cortex slice. Br J Pharmacol. 1988 Apr;93(4):846–854. doi: 10.1111/j.1476-5381.1988.tb11471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. de Belleroche J., Gardiner I. M. Muscarinic receptors discriminated by pirenzepine are involved in the regulation of neurotransmitter release in rat nucleus accumbens. Br J Pharmacol. 1985 Oct;86(2):505–508. doi: 10.1111/j.1476-5381.1985.tb08921.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES