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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Oct;110(2):910–916. doi: 10.1111/j.1476-5381.1993.tb13899.x

Evidence that M1 muscarinic receptors enhance noradrenaline release in mouse atria by activating protein kinase C.

M Costa 1, M Barrington 1, H Majewski 1
PMCID: PMC2175939  PMID: 7694761

Abstract

1. The M1 selective muscarinic agonist, McNeil A 343, enhanced the electrically evoked release of noradrenaline from postganglionic sympathetic nerves in mouse atria. This has been found previously to be due to activation of muscarinic receptors of the M1 subtype, probably located on sympathetic nerve terminals. The present study investigated the signal transduction mechanisms involved in the release-enhancing effects of McNeil A 343. The release of noradrenaline from mouse atria was assessed by measuring the electrically-induced (3 Hz, 60 s) outflow of radioactivity from atria which had been pre-incubated with [3H]-noradrenaline. 2. 8-Bromo cyclic AMP in the presence of IBMX was used to enhance maximally S-I noradrenaline release through cyclic AMP-dependent mechanisms. However, the facilitatory effect of McNeil A 343 (10 microM) was not different from the effect in the absence of these drugs, suggesting that McNeil A 343 enhances noradrenaline release independently of the cyclic AMP system. Furthermore, the release-enhancing effect of McNeil A 343 (10 microM) on noradrenaline release was also not altered by the 5-lipoxygenase inhibitor, BW A4C. 3. The facilitatory effect of McNeil A 343 was not altered in the presence of drugs (trifluoperazine, W7, and calmidazolium) which inhibit calmodulin-dependent processes, suggesting that the mechanisms of action of McNeil A 343 does not depend on calmodulin. 4. It was considered likely that the facilitatory effect of McNeil A 343 on noradrenaline release may be due to activation of protein kinase C, since activators of protein kinase C enhance noradrenaline release.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Allen G. S., Rand M. J., Story D. F. Effects of McN-A-343 and DMPP on the uptake and release of 3 H-noradrenaline by guinea-pig atria. Br J Pharmacol. 1972 Jul;45(3):480–489. doi: 10.1111/j.1476-5381.1972.tb08105.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen G. S., Rand M. J., Story D. F. Effects of the muscarinic agonist McN-A-343 on the release by sympathetic nerve stimulation of (3H)-noradrenaline from rabbit isolated ear arteries and guinea-pig atria. Br J Pharmacol. 1974 May;51(1):29–34. doi: 10.1111/j.1476-5381.1974.tb09628.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159–193. doi: 10.1146/annurev.bi.56.070187.001111. [DOI] [PubMed] [Google Scholar]
  4. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  5. Cost M., Majewski H. Evidence for facilitatory and inhibitory muscarinic receptors on postganglionic sympathetic nerves in mouse isolated atria. Br J Pharmacol. 1991 Apr;102(4):855–860. doi: 10.1111/j.1476-5381.1991.tb12266.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Costa M., Majewski H. Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, beta-adrenoceptors and angiotensin II receptors. Br J Pharmacol. 1988 Nov;95(3):993–1001. doi: 10.1111/j.1476-5381.1988.tb11730.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Costa M., Majewski H. Inhibitory prejunctional muscarinic receptors at sympathetic nerves do not operate through a cyclic AMP dependent pathway. Naunyn Schmiedebergs Arch Pharmacol. 1990 Dec;342(6):630–639. doi: 10.1007/BF00175705. [DOI] [PubMed] [Google Scholar]
  8. DeLorenzo R. J. The calmodulin hypothesis of neurotransmission. Cell Calcium. 1981 Aug;2(4):365–385. doi: 10.1016/0143-4160(81)90026-9. [DOI] [PubMed] [Google Scholar]
  9. Diamant S., Lev-Ari I., Uzielli I., Atlas D. Muscarinic agonists evoke neurotransmitter release: possible roles for phosphatidyl inositol bisphosphate breakdown products in neuromodulation. J Neurochem. 1988 Sep;51(3):795–802. doi: 10.1111/j.1471-4159.1988.tb01814.x. [DOI] [PubMed] [Google Scholar]
  10. Eglen R. M., Whiting R. L. Muscarinic receptor subtypes: a critique of the current classification and a proposal for a working nomenclature. J Auton Pharmacol. 1986 Dec;6(4):323–346. doi: 10.1111/j.1474-8673.1986.tb00661.x. [DOI] [PubMed] [Google Scholar]
  11. Fisher S. K., Agranoff B. W. Receptor activation and inositol lipid hydrolysis in neural tissues. J Neurochem. 1987 Apr;48(4):999–1017. doi: 10.1111/j.1471-4159.1987.tb05618.x. [DOI] [PubMed] [Google Scholar]
  12. Fozard J. R., Muscholl E. Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart. Br J Pharmacol. 1974 Apr;50(4):531–541. doi: 10.1111/j.1476-5381.1974.tb08586.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Greengard P. Neuronal phosphoproteins. Mediators of signal transduction. Mol Neurobiol. 1987 Spring-Summer;1(1-2):81–119. doi: 10.1007/BF02935265. [DOI] [PubMed] [Google Scholar]
  14. Göthert M., Hentrich F. Role of cAMP for regulation of impulse-evoked noradrenaline release from the rabbit pulmonary artery and its possible relationship to presynaptic ACTH receptors. Naunyn Schmiedebergs Arch Pharmacol. 1984 Dec;328(2):127–134. doi: 10.1007/BF00512061. [DOI] [PubMed] [Google Scholar]
  15. Habermeier-Muth A., Altes U., Forsyth K. M., Muscholl E. A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):483–489. doi: 10.1007/BF00169033. [DOI] [PubMed] [Google Scholar]
  16. Hanley M. R., Iversen L. L. Muscarinic cholinergic receptors in rat corpus striatum and regulation of guanosine cyclic 3',5'-monophosphate. Mol Pharmacol. 1978 Mar;14(2):246–255. [PubMed] [Google Scholar]
  17. Hedqvist P. Basic mechanisms of prostaglandin action on autonomic neurotransmission. Annu Rev Pharmacol Toxicol. 1977;17:259–279. doi: 10.1146/annurev.pa.17.040177.001355. [DOI] [PubMed] [Google Scholar]
  18. Hidaka H., Asano M., Tanaka T. Activity-structure relationship of calmodulin antagonists, Naphthalenesulfonamide derivatives. Mol Pharmacol. 1981 Nov;20(3):571–578. [PubMed] [Google Scholar]
  19. Jinnai K., Takahashi K., Fujita T. Enhancement of spontaneous acetylcholine release from motor nerve terminal by calmodulin inhibitors. Eur J Pharmacol. 1986 Nov 4;130(3):197–201. doi: 10.1016/0014-2999(86)90268-2. [DOI] [PubMed] [Google Scholar]
  20. Johnston H., Majewski H., Musgrave I. F. Involvement of cyclic nucleotides in prejunctional modulation of noradrenaline release in mouse atria. Br J Pharmacol. 1987 Aug;91(4):773–781. doi: 10.1111/j.1476-5381.1987.tb11275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Junstad M., Wennmalm A. Release of prostaglandin from the rabbit isolated heart following vagal nerve stimulation or acetylcholine infusion. Br J Pharmacol. 1974 Nov;52(3):375–379. doi: 10.1111/j.1476-5381.1974.tb08605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kase H., Iwahashi K., Nakanishi S., Matsuda Y., Yamada K., Takahashi M., Murakata C., Sato A., Kaneko M. K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. Biochem Biophys Res Commun. 1987 Jan 30;142(2):436–440. doi: 10.1016/0006-291x(87)90293-2. [DOI] [PubMed] [Google Scholar]
  23. Lenox R. H., Kant G. J., Meyerhoff J. L. Regional sensitivity of cyclic AMP and cyclic GMP in rat brain to central cholinergic stimulation. Life Sci. 1980 Jun 23;26(25):2201–2209. doi: 10.1016/0024-3205(80)90609-8. [DOI] [PubMed] [Google Scholar]
  24. Levin R. M., Weiss B. Selective binding of antipsychotics and other psychoactive agents to the calcium-dependent activator of cyclic nucleotide phosphodiesterase. J Pharmacol Exp Ther. 1979 Mar;208(3):454–459. [PubMed] [Google Scholar]
  25. Llinás R., McGuinness T. L., Leonard C. S., Sugimori M., Greengard P. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci U S A. 1985 May;82(9):3035–3039. doi: 10.1073/pnas.82.9.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Majewski H., Costa M., Foucart S., Murphy T. V., Musgrave I. F. Second messengers are involved in facilitatory but not inhibitory receptor actions at sympathetic nerve endings. Ann N Y Acad Sci. 1990;604:266–275. doi: 10.1111/j.1749-6632.1990.tb31999.x. [DOI] [PubMed] [Google Scholar]
  27. Malik K. U., Sehic E. Prostaglandins and the release of the adrenergic transmitter. Ann N Y Acad Sci. 1990;604:222–236. doi: 10.1111/j.1749-6632.1990.tb31996.x. [DOI] [PubMed] [Google Scholar]
  28. Matthies H. J., Palfrey H. C., Hirning L. D., Miller R. J. Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release. J Neurosci. 1987 Apr;7(4):1198–1206. doi: 10.1523/JNEUROSCI.07-04-01198.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mitchelson F. Muscarinic receptor differentiation. Pharmacol Ther. 1988;37(3):357–423. doi: 10.1016/0163-7258(88)90005-8. [DOI] [PubMed] [Google Scholar]
  30. Muscholl E. Peripheral muscarinic control of norepinephrine release in the cardiovascular system. Am J Physiol. 1980 Dec;239(6):H713–H720. doi: 10.1152/ajpheart.1980.239.6.H713. [DOI] [PubMed] [Google Scholar]
  31. Musgrave I. F., Foucart S., Majewski H. Evidence that angiotensin II enhances noradrenaline release from sympathetic nerves in mouse atria by activating protein kinase C. J Auton Pharmacol. 1991 Aug;11(4):211–220. doi: 10.1111/j.1474-8673.1991.tb00319.x. [DOI] [PubMed] [Google Scholar]
  32. Musgrave I. F., Majewski H. Effect of phorbol esters and polymyxin B on modulation of noradrenaline release in mouse atria. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):48–53. doi: 10.1007/BF00165125. [DOI] [PubMed] [Google Scholar]
  33. Nakanishi S., Yamada K., Kase H., Nakamura S., Nonomura Y. K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase. J Biol Chem. 1988 May 5;263(13):6215–6219. [PubMed] [Google Scholar]
  34. Nathanson N. M. Molecular properties of the muscarinic acetylcholine receptor. Annu Rev Neurosci. 1987;10:195–236. doi: 10.1146/annurev.ne.10.030187.001211. [DOI] [PubMed] [Google Scholar]
  35. Nedergaard O. A. Modulation by the muscarinic agonist McN-A-343 of noradrenaline release from vascular sympathetic neurones. J Cardiovasc Pharmacol. 1980 Sep-Oct;2(5):629–643. doi: 10.1097/00005344-198009000-00012. [DOI] [PubMed] [Google Scholar]
  36. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  37. Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science. 1984 Sep 21;225(4668):1365–1370. doi: 10.1126/science.6147898. [DOI] [PubMed] [Google Scholar]
  38. Publicover S. J. Calmodulin, synchronous and asynchronous release of neurotransmitter. Comp Biochem Physiol A Comp Physiol. 1985;82(1):7–11. doi: 10.1016/0300-9629(85)90696-6. [DOI] [PubMed] [Google Scholar]
  39. Reimann W., Köllhofer U., Wagner B. W-7 at calmodulin-antagonistic concentrations facilitates noradrenaline release from rat brain cortex slices. Eur J Pharmacol. 1988 Mar 15;147(3):481–485. doi: 10.1016/0014-2999(88)90186-0. [DOI] [PubMed] [Google Scholar]
  40. Rüegg U. T., Burgess G. M. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci. 1989 Jun;10(6):218–220. doi: 10.1016/0165-6147(89)90263-0. [DOI] [PubMed] [Google Scholar]
  41. Tateson J. E., Randall R. W., Reynolds C. H., Jackson W. P., Bhattacherjee P., Salmon J. A., Garland L. G. Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessment in vitro and ex vivo. Br J Pharmacol. 1988 Jun;94(2):528–539. doi: 10.1111/j.1476-5381.1988.tb11557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vizi E. S., Kobayashi O., Töröcsik A., Kinjo M., Nagashima H., Manabe N., Goldiner P. L., Potter P. E., Foldes F. F. Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release. Neuroscience. 1989;31(1):259–267. doi: 10.1016/0306-4522(89)90048-1. [DOI] [PubMed] [Google Scholar]
  43. Xu M., Yamamoto T., Kato T. In vivo striatal dopamine release by M1 muscarinic receptors is induced by activation of protein kinase C. J Neurochem. 1990 Jun;54(6):1917–1919. doi: 10.1111/j.1471-4159.1990.tb04891.x. [DOI] [PubMed] [Google Scholar]
  44. Young S., Parker P. J., Ullrich A., Stabel S. Down-regulation of protein kinase C is due to an increased rate of degradation. Biochem J. 1987 Jun 15;244(3):775–779. doi: 10.1042/bj2440775. [DOI] [PMC free article] [PubMed] [Google Scholar]

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