Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1972 Nov;69(11):3287–3291. doi: 10.1073/pnas.69.11.3287

Role of Muscarinic Cholinergic Receptors in Regulation of Guanosine 3′:5′-Cyclic Monophosphate Content in Mammalian Brain, Heart Muscle, and Intestinal Smooth Muscle

Tee-Ping Lee 1, J F Kuo 1, Paul Greengard 1,*
PMCID: PMC389755  PMID: 4343961

Abstract

Effects of acetylcholine and of agents that mimic or block its physiological actions have been studied upon concentrations of guanosine 3′:5′-cyclic monophosphate (cyclic GMP) and adenosine 3′:5′-cyclic monophosphate (cyclic AMP) in slices of mammalian cerebral cortex, heart ventricle, and ileum. Acetylcholine, and cholinomimetic agents with a predominantly muscarinic action, such as methacholine, bethanechol, and pilocarpine, induced an increase in the concentration of cyclic GMP, accompanied by no change or a slight decrease in the concentration of cyclic AMP, in all three tissues studied. Tetramethylammonium, a cholinomimetic agent with a predominantly nicotinic action, on the other hand, did not significantly alter concentrations of either cyclic GMP or cyclic AMP. The increase in the tissue content of cyclic GMP induced by acetylcholine and its muscarinic analogs was antagonized by atropine, a muscarinic blocking agent, but not by hexamethonium, a nicotinic blocking agent.

These and other results suggest the generalization that the interaction of acetylcholine with muscarinic receptors, but not with nicotinic receptors, causes an increase in the concentration of cyclic GMP. The data are compatible with the hypothesis that cyclic GMP may mediate the muscarinic actions of acetylcholine.

The antagonistic actions of cholinergic and adrenergic agents on the physiology of contraction of intestinal smooth muscle and of cardiac muscle are reflected in, and may result from, antagonistic actions of these compounds on the levels of both cyclic GMP and cyclic AMP in these tissues.

Keywords: cyclic AMP, nicotine receptors, atropine

Full text

PDF
3287

Selected References

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

  1. ASHMAN D. F., LIPTON R., MELICOW M. M., PRICE T. D. Isolation of adenosine 3', 5'-monophosphate and guanosine 3', 5'-monophosphate from rat urine. Biochem Biophys Res Commun. 1963 May 22;11:330–334. doi: 10.1016/0006-291x(63)90566-7. [DOI] [PubMed] [Google Scholar]
  2. Beavo J. A., Hardman J. G., Sutherland E. W. Hydrolysis of cyclic guanosine and adenosine 3',5'-monophosphates by rat and bovine tissues. J Biol Chem. 1970 Nov 10;245(21):5649–5655. [PubMed] [Google Scholar]
  3. Ferrendelli J. A., Steiner A. L., McDougal D. B., Jr, Kipnis D. M. The effect of oxotremorine and atropine on cGMP and cAMP levels in mouse cerebral cortex and cerebellum. Biochem Biophys Res Commun. 1970 Nov 25;41(4):1061–1067. doi: 10.1016/0006-291x(70)90193-2. [DOI] [PubMed] [Google Scholar]
  4. George W. J., Polson J. B., O'Toole A. G., Goldberg N. D. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci U S A. 1970 Jun;66(2):398–403. doi: 10.1073/pnas.66.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldberg N. D., Dietz S. B., O'Toole A. G. Cyclic guanosine 3',5'-monophosphate in mammalian tissues and urine. J Biol Chem. 1969 Aug 25;244(16):4458–4466. [PubMed] [Google Scholar]
  6. Hardman J. G., Davis J. W., Sutherland E. W. Measurement of guanosine 3',5'-monophosphate and other cyclic nucleotides. Variations in urinary excretion with hormonal state of the rat. J Biol Chem. 1966 Oct 25;241(20):4812–4815. [PubMed] [Google Scholar]
  7. Hardman J. G., Sutherland E. W. Guanyl cyclase, an enzyme catalyzing the formation of guanosine 3',5'-monophosphate from guanosine trihosphate. J Biol Chem. 1969 Dec 10;244(23):6363–6370. [PubMed] [Google Scholar]
  8. Ishikawa E., Ishikawa S., Davis J. W., Sutherland E. W. Determination of guanosine 3',5'-monophosphate in tissues and of guanyl cyclase in rat intestine. J Biol Chem. 1969 Dec 10;244(23):6371–6376. [PubMed] [Google Scholar]
  9. Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. 8. An assay method for the measurement of adenosine 3',5'-monophosphate in various tissues and a study of agents influencing its level in adipose cells. J Biol Chem. 1970 Aug 25;245(16):4067–4073. [PubMed] [Google Scholar]
  10. Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3',5'-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1349–1355. doi: 10.1073/pnas.64.4.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. VI. Isolation and partial purification of a protein kinase activated by guanosine 3',5'-monophosphate. J Biol Chem. 1970 May 25;245(10):2493–2498. [PubMed] [Google Scholar]
  12. Kuo J. F., Lee T. P., Reyes P. L., Walton K. G., Donnelly T. E., Jr, Greengard P. Cyclic nucleotide-dependent protein kinases. X. An assay method for the measurement of quanosine 3',5'-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J Biol Chem. 1972 Jan 10;247(1):16–22. [PubMed] [Google Scholar]
  13. Kuo J. F., Wyatt G. R., Greengard P. Cyclic nucleotide-dependent protein kinases. IX. Partial purification and some properties of guanosine 3',5'-monophosphate-dependent and adenosine 3',5'-monophosphate-dependent protein kinases from various tissues and species of Arthropoda. J Biol Chem. 1971 Dec 10;246(23):7159–7167. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lee T. P., Kuo J. F., Greengard P. Regulation of myocardial cyclic AMP by isoproterenol, glucagon and acetylcholine. Biochem Biophys Res Commun. 1971 Nov;45(4):991–997. doi: 10.1016/0006-291x(71)90435-9. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES