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. 1970 Dec;40(4):668–688. doi: 10.1111/j.1476-5381.1970.tb10646.x

Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut

G Burnstock, G Campbell, D Satchell, Anne Smythe
PMCID: PMC1702901  PMID: 4322041

Abstract

1. Stimulation of the vagal non-adrenergic inhibitory innervation caused the release of adenosine and inosine into vascular perfusates from the stomachs of guinea-pigs and toads.

2. Stimulation of portions of Auerbach's plexus isolated from turkey gizzard caused the release of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP).

3. ATP, added to solutions perfused through the toad stomach vasculature, was broken down to adenosine, inosine and adenine.

4. Of a series of purine and pyrimidine derivatives tested for inhibitory activity on the guinea-pig isolated taenia coli, ATP and ADP were the most potent.

5. ATP caused inhibition of twelve other gut preparations previously shown to contain non-adrenergic inhibitory nerves. The inhibitory action of ATP was not prevented by tetrodotoxin.

6. Quinidine antagonized relaxations of the guinea-pig taenia coli caused by catecholamines or adrenergic nerve stimulation. Higher concentrations of quinidine antagonized relaxations caused by ATP or non-adrenergic inhibitory nerve stimulation.

7. When tachyphylaxis to ATP had been produced in the rabbit ileum, there was a consistent depression of the responses to non-adrenergic inhibitory nerve stimulation but not of responses to adrenergic nerve stimulation.

8. It is suggested that ATP or a related nucleotide is the transmitter substance released by the non-adrenergic inhibitory innervation of the gut.

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Selected References

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

  1. ABOOD L. G., KOKETSU K., MIYAMOTO S. Outflux of various phosphates during membrane depolarization of excitable tissues. Am J Physiol. 1962 Mar;202:469–474. doi: 10.1152/ajplegacy.1962.202.3.469. [DOI] [PubMed] [Google Scholar]
  2. Ambache N., Freeman M. A. Atropine-resistant longitudinal muscle spasms due to excitation of non-cholinergic neurones in Auerbach's plexus. J Physiol. 1968 Dec;199(3):705–727. doi: 10.1113/jphysiol.1968.sp008674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Axelsson J., Holmberg B. The effects of extracellularly applied ATP and related compounds on electrical and mechanical activity of the smooth muscle taenia coli from the guinea-pig. Acta Physiol Scand. 1969 Jan-Feb;75(1):149–156. doi: 10.1111/j.1748-1716.1969.tb04366.x. [DOI] [PubMed] [Google Scholar]
  4. BRECHT K., EPPLE O. Uber die Wirkung von Acetylcholin und Adenosintriposphat auf isolierte lebende und mit Wasser-Glycerin extrahierte quergestreifte und glatte Muskeln des Frosches. Pflugers Arch. 1952 Jul;225(4):315–326. doi: 10.1007/BF00370176. [DOI] [PubMed] [Google Scholar]
  5. BULBRING E. Measurements of oxygen consumption in smooth muscle. J Physiol. 1953 Oct;122(1):111–134. doi: 10.1113/jphysiol.1953.sp004983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BURN J. H., GIBBONS W. R. THE PART PLAYED BY CALCIUM IN DETERMINING THE RESPONSE TO STIMULATION OF SYMPATHETIC POSTGANGLIONIC FIBRES. Br J Pharmacol Chemother. 1964 Jun;22:540–548. doi: 10.1111/j.1476-5381.1964.tb01708.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. BURNSTOCK G., CAMPBELL G., BENNETT M., HOLMAN M. E. INNERVATION OF THE GUINEA-PIG TAENIA COLI: ARE THERE INTRINSIC INHIBITORY NERVES WHICH ARE DISTINCT FROM SYMPATHETIC NERVES? Int J Neuropharmacol. 1964 May;3:163–166. doi: 10.1016/0028-3908(64)90003-6. [DOI] [PubMed] [Google Scholar]
  8. Barsoum G. S., Gaddum J. H. The pharmacological estimation of adenosine and histamine in blood. J Physiol. 1935 Aug 22;85(1):1–14. doi: 10.1113/jphysiol.1935.sp003298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bell C. Differential effects of tetrodotoxin on sympathomimetic actions of nicotine and tyramine. Br J Pharmacol Chemother. 1968 Jan;32(1):96–103. doi: 10.1111/j.1476-5381.1968.tb00433.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bennett M. R., Burnstock G., Holman M. Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli. J Physiol. 1966 Feb;182(3):541–558. doi: 10.1113/jphysiol.1966.sp007836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bennett M. R., Merrillees N. C. An analysis of the transmission of excitation from autonomic nerves to smooth muscle. J Physiol. 1966 Aug;185(3):520–535. doi: 10.1113/jphysiol.1966.sp008000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bennett M. R. Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves. J Physiol. 1966 Jul;185(1):124–131. doi: 10.1113/jphysiol.1966.sp007975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bennett M. R., Rogers D. C. A study of the innervation of the taenia coli. J Cell Biol. 1967 Jun;33(3):573–596. doi: 10.1083/jcb.33.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Bennett M. R. The effect of intracellular current pulses in smooth muscle cells of the guinea pig vas deferens at rest and during transmission. J Gen Physiol. 1967 Nov;50(10):2459–2475. doi: 10.1085/jgp.50.10.2459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bennett T. Nerve-mediated excitation and inhibition of the smooth muscle cells of the avian gizzard. J Physiol. 1969 Oct;204(3):669–686. doi: 10.1113/jphysiol.1969.sp008938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bowman W. C., Hall M. T. Inhibition of rabbit intestine mediated by alpha- and beta-adrenoceptors. Br J Pharmacol. 1970 Feb;38(2):399–415. doi: 10.1111/j.1476-5381.1970.tb08528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Burnstock G., Campbell G., Rand M. J. The inhibitory innervation of the taenia of the guinea-pig caecum. J Physiol. 1966 Feb;182(3):504–526. doi: 10.1113/jphysiol.1966.sp007834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Bülbring E., Gershon M. D. 5-hydroxytryptamine participation in the vagal inhibitory innervation of the stomach. J Physiol. 1967 Oct;192(3):823–846. doi: 10.1113/jphysiol.1967.sp008334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. CAMPBELL G., BURNSTOCK G., WOOD M. A METHOD FOR DISTINGUISHING BETWEEN ADRENERGIC AND CHOLINERGIC EXCITATORY INNERVATION OF SMOOTH MUSCLE. Q J Exp Physiol Cogn Med Sci. 1964 Jul;49:268–276. doi: 10.1113/expphysiol.1964.sp001731. [DOI] [PubMed] [Google Scholar]
  20. Campbell G. Nerve-mediated excitation of the taenia of the guinea-pig caecum. J Physiol. 1966 Jul;185(1):148–159. doi: 10.1113/jphysiol.1966.sp007977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Campbell G. The autonomic innervation of the stomach of a toad (Bufo marinus). Comp Biochem Physiol. 1969 Dec 1;31(5):693–706. doi: 10.1016/0010-406x(69)92069-6. [DOI] [PubMed] [Google Scholar]
  22. Campbell G. The inhibitory nerve fibres in the vagal supply to the guinea-pig stomach. J Physiol. 1966 Aug;185(3):600–612. doi: 10.1113/jphysiol.1966.sp008004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Day M. D., Warren P. R. A pharmacological analysis of the responses to transmural stimulation in isolated intestinal preparations. Br J Pharmacol Chemother. 1968 Feb;32(2):227–240. doi: 10.1111/j.1476-5381.1968.tb00967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Drury A. N., Szent-Györgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol. 1929 Nov 25;68(3):213–237. doi: 10.1113/jphysiol.1929.sp002608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. EWING P. L., SCHLENK F., EMERSON G. A. Comparison of smooth muscle effects of crotonoside (isoguanosine) and adenosine. J Pharmacol Exp Ther. 1949 Nov;97(3):379–383. [PubMed] [Google Scholar]
  27. Furness J. B. An electrophysiological study of the innervation of the smooth muscle of the colon. J Physiol. 1969 Dec;205(3):549–562. doi: 10.1113/jphysiol.1969.sp008982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. GINSBORG B. L. Spontaneous activity in muscle fibres of the chick. J Physiol. 1960 Mar;150:707–717. doi: 10.1113/jphysiol.1960.sp006413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. GREEFF K., HOLTZ P. Untersuchungen am isolierten Vagus-Magenpräparat. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1956;227(5):427–435. [PubMed] [Google Scholar]
  30. HOLMAN M. E., HUGHES J. R. INHIBITION OF INTESTINAL SMOOTH MUSCLE. Aust J Exp Biol Med Sci. 1965 Jun;43:277–290. doi: 10.1038/icb.1965.27. [DOI] [PubMed] [Google Scholar]
  31. HOLTON F. A., HOLTON P. The capillary dilator substances in dry powders of spinal roots; a possible role of adenosine triphosphate in chemical transmission from nerve endings. J Physiol. 1954 Oct 28;126(1):124–140. doi: 10.1113/jphysiol.1954.sp005198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. HOLTON P. The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol. 1959 Mar 12;145(3):494–504. doi: 10.1113/jphysiol.1959.sp006157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Heazell M. A. A non-adrenergic component to the inhibitory innervation of the fundus of the rat stomach. Br J Pharmacol. 1969 May;36(1):186P–187P. [PMC free article] [PubMed] [Google Scholar]
  34. Imai S., Takeda K. Effect of vasodilators upon the isolated taenia coli of the guinea pig. J Pharmacol Exp Ther. 1967 Jun;156(3):557–564. [PubMed] [Google Scholar]
  35. Kim T. S., Shulman J., Levine R. A. Relaxant effect of cyclic adenosine 3',5'-monophosphate on the isolated rabbit ileum. J Pharmacol Exp Ther. 1968 Sep;163(1):36–42. [PubMed] [Google Scholar]
  36. Lunde P. K., Waaler B. A., Walloe L. The inhibitory effect of various phenols upon ATP-induced vasoconstriction in isolated perfused rabbit lungs. Acta Physiol Scand. 1968 Mar;72(3):331–337. doi: 10.1111/j.1748-1716.1968.tb03855.x. [DOI] [PubMed] [Google Scholar]
  37. MADINAVEITIA J., RAVENTOS J. Antimalarial compounds as antagonists of adenosine. Br J Pharmacol Chemother. 1949 Mar;4(1):81–92. doi: 10.1111/j.1476-5381.1949.tb00518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. MALINOVSKY L. The nerve supply of the stomach in the domestic pigeon (Columba domestica). Cesk Morfol. 1963;11:16–27. [PubMed] [Google Scholar]
  39. MIHICH E., CLARKE D. A., PHILIPS F. S. Effect of adenosine analogs on isolated intestine and uterus. J Pharmacol Exp Ther. 1954 Jul;111(3):335–342. [PubMed] [Google Scholar]
  40. MOULTON R., SPECTOR W. G., WILLOUGHBY D. A. Histamine release and pain production by xanthosine and related compounds. Br J Pharmacol Chemother. 1957 Sep;12(3):365–370. doi: 10.1111/j.1476-5381.1957.tb00150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mal'chikova L. S., Poskonova M. A. Vliianie adrenalina i adenilovykh nukleozidov na spontannuiu aktivnost' i atsetilkholinovuiu kontrakturu gladkikh myshts. Fiziol Zh SSSR Im I M Sechenova. 1969 Nov;55(11):1378–1384. [PubMed] [Google Scholar]
  42. Martinson J. Vagal relaxation of the stomach. Experimental re-investigation of the concept of the transmission mechanism. Acta Physiol Scand. 1965 Aug;64(4):453–462. doi: 10.1111/j.1748-1716.1965.tb04204.x. [DOI] [PubMed] [Google Scholar]
  43. NAESS K., SCHANCHE S. The action of barbiturates on the intestine. Acta Pharmacol Toxicol (Copenh) 1957;13(1):90–95. doi: 10.1111/j.1600-0773.1957.tb00242.x. [DOI] [PubMed] [Google Scholar]
  44. Ohga A., Nakazato Y., Saito K. An analysis of the vago-vagal reflex relaxation of the stomach. Nihon Seirigaku Zasshi. 1969;31(2):92–93. [PubMed] [Google Scholar]
  45. PATON W. D., VANE J. R. Analysis of he responses of the isolated stomach to electrical stimulation and to drugs. J Physiol. 1963 Jan;165:10–46. doi: 10.1113/jphysiol.1963.sp007040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rogers D. C., Burnstock G. Muliaxonal autonomic junctions in intestinal smooth muscle of the toad (Bufo marinus). J Comp Neurol. 1966 Apr;126(4):625–652. [PubMed] [Google Scholar]
  47. WOOD T. A reagent for the detection of chloride and of certain purines and pyrimidines on paper chromatograms. Nature. 1955 Jul 23;176(4473):175–176. doi: 10.1038/176175a0. [DOI] [PubMed] [Google Scholar]

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