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. 1974 May 1;63(5):609–624. doi: 10.1085/jgp.63.5.609

A Cyclic Adenosine Monophosphate Link in the Catecholamine Enhancement of Transmitter Release at the Neuromuscular Junction

Michael D Miyamoto 1, Bruce McL Breckenridge 1
PMCID: PMC2203569  PMID: 4363380

Abstract

The frequency of miniature endplate potentials (mepps) in rat diaphragms was markedly increased by epinephrine and norepinephrine in preparations exposed to 15 mM K+. The effect was rapid in onset but gradually declined during continued exposure to the catecholamines. N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl-cAMP) also caused transient frequency increases resembling in time-course those observed with catecholamines. Contrary to previous reports, catecholamines and dibutyryl-cAMP had little effect on mepp frequency in preparations not treated with K+. Sustained increases with theophylline and decreases with adenosine were found in both K+-treated and untreated preparations. Analysis of the data obtained with catecholamines showed the intensity of the response to be a function of nerve terminal polarization. The inability of catecholamines and dibutyryl-cAMP to affect mepp frequency of untreated preparations argues against an obligatory role for cAMP in the neurosecretory mechanism. The findings are consistent with an action of catecholamines and cAMP in the regulation of transmitter release at fatigued preparations.

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Selected References

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  1. BOWMAN W. C., RAPER C. THE EFFECTS OF ADRENALINE AND OTHER DRUGS AFFECTING CARBOHYDRATE METABOLISM ON CONTRACTIONS OF THE RAT DIAPHRAGM. Br J Pharmacol Chemother. 1964 Aug;23:184–200. doi: 10.1111/j.1476-5381.1964.tb01578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blinks J. R., Olson C. B., Jewell B. R., Bravený P. Influence of caffeine and other methylxanthines on mechanical properties of isolated mammalian heart muscle. Evidence for a dual mechanism of action. Circ Res. 1972 Apr;30(4):367–392. doi: 10.1161/01.res.30.4.367. [DOI] [PubMed] [Google Scholar]
  3. Bowman W. C., Nott M. W. Actions of sympathomimetic amines and their antagonists on skeletal muscle. Pharmacol Rev. 1969 Mar;21(1):27–72. [PubMed] [Google Scholar]
  4. Bradham L. S., Holt D. A., Sims M. The effect of Ca2+ on the adenyl cyclase of calf brain. Biochim Biophys Acta. 1970 Feb 24;201(2):250–260. doi: 10.1016/0304-4165(70)90299-0. [DOI] [PubMed] [Google Scholar]
  5. Breckenridge B. M., Burn J. H., Matschinsky F. M. Theophylline, epinephrine, and neostigmine facilitation of neuromuscular transmission. Proc Natl Acad Sci U S A. 1967 Jun;57(6):1893–1897. doi: 10.1073/pnas.57.6.1893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooke J. D., Quastel D. M. Transmitter release by mammalian motor nerve terminals in response to focal polarization. J Physiol. 1973 Jan;228(2):377–405. doi: 10.1113/jphysiol.1973.sp010092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FATT P., KATZ B. Spontaneous subthreshold activity at motor nerve endings. J Physiol. 1952 May;117(1):109–128. [PMC free article] [PubMed] [Google Scholar]
  8. Ginsborg B. L., Hirst G. D. The effect of adenosine on the release of the transmitter from the phrenic nerve of the rat. J Physiol. 1972 Aug;224(3):629–645. doi: 10.1113/jphysiol.1972.sp009916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldberg A. L., Singer J. J. Evidence for a role of cyclic AMP in neuromuscular transmission. Proc Natl Acad Sci U S A. 1969 Sep;64(1):134–141. doi: 10.1073/pnas.64.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hubbard J. I., Jones S. F., Landau E. M. An examination of the effects of osmotic pressure changes upon transmitter release from mammalian motor nerve terminals. J Physiol. 1968 Aug;197(3):639–657. doi: 10.1113/jphysiol.1968.sp008579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jenkinson D. H., Stamenović B. A., Whitaker B. D. The effect of noradrenaline on the end-plate potential in twitch fibres of the frog. J Physiol. 1968 Apr;195(3):743–754. doi: 10.1113/jphysiol.1968.sp008486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KRNJEVIC K., MILEDI R. Some effects produced by adrenaline upon neuromuscular propagation in rats. J Physiol. 1958 Apr 30;141(2):291–304. doi: 10.1113/jphysiol.1958.sp005974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kakiuchi S., Rall T. W. Studies on adenosine 3',5'-phosphate in rabbit cerebral cortex. Mol Pharmacol. 1968 Jul;4(4):379–388. [PubMed] [Google Scholar]
  14. Katz B., Miledi R. Further study of the role of calcium in synaptic transmission. J Physiol. 1970 May;207(3):789–801. doi: 10.1113/jphysiol.1970.sp009095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kuba K. Effects of catecholamines on the neuromuscular junction in the rat diaphragm. J Physiol. 1970 Dec;211(3):551–570. doi: 10.1113/jphysiol.1970.sp009293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuba K., Tomita T. Effects of noradrenaline on miniature end-plate potentials and on end-plate potential. J Theor Biol. 1972 Jul;36(1):81–88. doi: 10.1016/0022-5193(72)90178-6. [DOI] [PubMed] [Google Scholar]
  17. LILEY A. W. The effects of presynaptic polarization on the spontaneous activity at the mammalian neuromuscular junction. J Physiol. 1956 Nov 28;134(2):427–443. doi: 10.1113/jphysiol.1956.sp005655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McKenzie S. G., Bär H. P. On the mechanism of adenyl cyclase inhibition by adenosine. Can J Physiol Pharmacol. 1973 Mar;51(3):190–196. doi: 10.1139/y73-027. [DOI] [PubMed] [Google Scholar]
  19. Miyamoto E., Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. 3. Purification and properties of adenosine 3',5'-monophosphate-dependent protein kinase from bovine brain. J Biol Chem. 1969 Dec 10;244(23):6395–6402. [PubMed] [Google Scholar]
  20. Pappano A. J. Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ Res. 1970 Sep;27(3):379–390. doi: 10.1161/01.res.27.3.379. [DOI] [PubMed] [Google Scholar]
  21. Rasmussen H. Cell communication, calcium ion, and cyclic adenosine monophosphate. Science. 1970 Oct 23;170(3956):404–412. doi: 10.1126/science.170.3956.404. [DOI] [PubMed] [Google Scholar]
  22. Riddick D. H., Kregenow F. M., Orloff J. The effect of norepinephrine and dibutyryl cyclic adenosine monophosphate on cation transport in duck erythrocytes. J Gen Physiol. 1971 Jun;57(6):752–766. doi: 10.1085/jgp.57.6.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sattin A., Rall T. W. The effect of adenosine and adenine nucleotides on the cyclic adenosine 3', 5'-phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol. 1970 Jan;6(1):13–23. [PubMed] [Google Scholar]
  24. Sutherland E. W., Robison G. A. The role of cyclic-3',5'-AMP in responses to catecholamines and other hormones. Pharmacol Rev. 1966 Mar;18(1):145–161. [PubMed] [Google Scholar]
  25. Varagić V. M., Zugić M. Interactions of xanthine derivatives, catecholamines and glucose-6-phosphate on the isolated phrenic nerve diaphragm preparation of the rat. Pharmacology. 1971;5(5):275–286. doi: 10.1159/000136200. [DOI] [PubMed] [Google Scholar]

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