Hostname: page-component-8448b6f56d-dnltx Total loading time: 0 Render date: 2024-04-18T10:20:20.854Z Has data issue: false hasContentIssue false
  • English
  • Français

The Concept of Cotransmission: Focus on ATP as a Cotransmitter and its Significance in Health and Disease

Published online by Cambridge University Press:  26 February 2014

Geoffrey Burnstock
Geoffrey Burnstock*
Affiliation:
Autonomic Neuroscience Centre, University College Medical School, Rowland Hill Street, London NW3 2PF, UKand Department of Pharmacology, The University of Melbourne, Melbourne, Australia. E-mail: g.burnstock@ucl.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

The concept of cotransmission, including sympathetic nerve release of noradrenaline and ATP, was formalised in 1976, which challenged the accepted view known as ‘Dale's Principle’ that one nerve released only one transmitter. ATP was also shown to be a cotransmitter with acetylcholine in parasympathetic nerves supplying the urinary bladder and as a cotransmitter with nitric oxide in non-adrenergic, non-cholinergic inhibitory nerves supplying the intestine. It is now recognised that ATP is a cotransmitter in most, if not all, nerves in the peripheral and central nervous systems. The physiological significance of cotransmission will be considered. In pathophysiology, the role of ATP as a cotransmitter appears to increase as shown, for example, in the parasympathetic nerves supplying the diseased human bladder and in sympathetic nerves in spontaneously hypertensive rats. ATP is likely to be involved in sympathetic pain, causalgia and reflex sympathetic dystrophy. Purinergic signalling also appears to be enhanced in inflammatory and stress conditions.

Type
The Erasmus Lecture 2012
Information
European Review , Volume 22 , Issue 1 , February 2014 , pp. 1 - 17
Copyright
Copyright © Academia Europaea 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Eccles, J. C. (1957) The clinical significance of research work on the chemical transmitter substances of the nervous system. Medical Journal of Australia, 44, pp. 745–753.Google Scholar
2.Dale, H. (1935) Pharmacology and nerve endings. Proceedings of the Royal Society of Medicine, 28, pp. 319–332.Google Scholar
3.Burnstock, G., Campbell, G., Bennett, M. and Holman, M. E. (1964) Innervation of the guinea-pig taenia coli: are there intrinsic inhibitory nerves which are distinct from sympathetic nerves? International Journal of Neuropharmacology, 3, pp. 163–166.Google Scholar
4.Burnstock, G. (1969) Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacological Reviews, 21, pp. 247–324.Google Scholar
5.Eccles, J. C. (1964) The Physiology of Synapses (Berlin: Springer Verlag).Google Scholar
6.Drury, N. and Szent-Györgyi, A. (1929) The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. Journal of Physiology, 68, pp. 213–237.Google Scholar
7.Holton, P. (1959) The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. Journal of Physiology, 145, pp. 494–504.Google Scholar
8.Burnstock, G., Campbell, G., Satchell, D. and Smythe, A. (1970) Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. British Journal of Pharmacology, 40, pp. 668–688.Google Scholar
9.Burnstock, G. (1972) Purinergic nerves. Pharmacology Review, 24, pp. 509–581.Google ScholarPubMed
10.Abbracchio, M. P. and Burnstock, G. (1994) Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacology & Therapeutics, 64, pp. 445–475.Google Scholar
11.Ralevic, V. and Burnstock, G. (1998) Receptors for purines and pyrimidines. Pharmacological Reviews, 50, pp. 413–492.Google Scholar
12.Burnstock, G. (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiological Reviews, 87, 659–797.Google Scholar
13.Burnstock, G. and Verkhratsky, A. (2009) Evolutionary origins of the purinergic signalling system. Acta Physiologica, 195, pp. 415–447.Google Scholar
14.Su, C., Bevan, J. A. and Burnstock, G. (1971) [3H]adenosine triphosphate: release during stimulation of enteric nerves. Science, 173, pp. 337–339.CrossRefGoogle Scholar
15.Stjärne, L. and Lishajko, F. (1966) Comparison of spontaneous loss of catecholamines and ATP in vitro from isolated bovine adrenomedullary, vesicular gland, vas deferens and splenic nerve granules. Journal of Neurochemistry, 13, pp. 1213–1216.Google Scholar
16.Nakanishi, H. and Takeda, H. (1973) The possible role of adenosine triphosphate in chemical transmission between the hypogastric nerve terminal and seminal vesicle in the guinea-pig. Japanese Journal of Pharmacology, 23, pp. 479–490.Google Scholar
17.Langer, S. Z. and Pinto, J. E. B. (1976) Possible involvement of a transmitter different from norepinephrine in residual responses to nerve stimulation of cat nictitating membrane after pretreatment with reserpine. Journal of Pharmacology & Experimental Therapeutics, 196, pp. 697–713.Google Scholar
18.Burnstock, G. (1976) Do some nerve cells release more than one transmitter? Neuroscience, 1, pp. 239–248.Google Scholar
19.Burnstock, G. and Holman, M. E. (1961) The transmission of excitation from autonomic nerve to smooth muscle. Journal of Physiology, 155, pp. 115–133.Google Scholar
20.Kasakov, L. and Burnstock, G. (1983) The use of the slowly degradable analog, α,β-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder. European Journal of Pharmacology, 86, pp. 291–294.Google Scholar
21.Sneddon, P. and Burnstock, G. (1984) Inhibition of excitatory junction potentials in guinea-pig vas deferens by α,β-methylene-ATP: further evidence for ATP and noradrenaline as cotransmitters. European Journal of Pharmacology, 100, pp. 85–90.CrossRefGoogle ScholarPubMed
22.Westfall, D. P., Stitzel, R. E. and Rowe, J. N. (1978) The postjunctional effects and neural release of purine compounds in the guinea-pig vas deferens. European Journal of Pharmacology, 50, pp. 27–38.CrossRefGoogle ScholarPubMed
23.Neild, T. O. and Hirst, G. D. S. (1984) The ‘γ-connection’: a reply. Trends in Pharmacological Sciences, 5, pp. 56–57.Google Scholar
24.Kirkpatrick, K. and Burnstock, G. (1987) Sympathetic nerve-mediated release of ATP from the guinea-pig vas deferens is unaffected by reserpine. European Journal of Pharmacology, 138, pp. 207–214.Google Scholar
25.Sneddon, P. and Burnstock, G. (1984) ATP as a co-transmitter in rat tail artery. European Journal of Pharmacology, 106, pp. 149–152.Google Scholar
26.Burnstock, G. (1990) Noradrenaline and ATP as cotransmitters in sympathetic nerves. Neurochemistry International, 17, 357–368.Google Scholar
27.Burnstock, G. (1995) Noradrenaline and ATP: cotransmitters and neuromodulators. Journal of Physiology & Pharmacology, 46, pp. 365–384.Google Scholar
28.Katsuragi, T. and Su, C. (1982) Augmentation by theophylline of [3H]purine release from vascular adrenergic nerves: evidence for presynaptic autoinhibition. Journal of Pharmacology & Experimental Therapeutics, 220, pp. 152–156.Google Scholar
29.Cheung, D. W. (1991) Neuropeptide Y potentiates specifically the purinergic component of the neural responses in the guinea-pig saphenous artery. Circulation Research, 68, pp. 1401–1407.Google Scholar
30.Ellis, J. L. and Burnstock, G. (1990) Neuropeptide Y neuromodulation of sympathetic co-transmission in the guinea-pig vas deferens. British Journal of Pharmacology, 100, pp. 457–462.CrossRefGoogle ScholarPubMed
31.Ramme, D., Regenold, J. T., Starke, K., Busse, R. and Illes, P. (1987) Identification of the neuroeffector transmitter in jejunal branches of the rabbit mesenteric artery. Naunyn Schmiedeberg's Archives of Pharmacology, 336, pp. 267–273.Google Scholar
32.Evans, R. J. and Surprenant, A. (1992) Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP. British Journal of Pharmacology, 106, pp. 242–249.Google Scholar
33.Furness, J. B., Morris, J. L., Gibbins, I. L. and Costa, M. (1989) Chemical coding of neurons and plurichemical transmission. Annual Review of Pharmacology & Toxicology, 29, pp. 289–306.Google Scholar
34.Burnstock, G. (1990) Co-transmission. The fifth Heymans memorial lecture – Ghent, February 17, 1990. Archives internationales de Pharmacodynamie et de Térapie, 304, pp. 7–33.Google Scholar
35.Burnstock, G. (2011) Therapeutic potential of purinergic signalling for diseases of the urinary tract. BJU International, 107, pp. 192–204.Google Scholar
36.Zhang, M., Zhong, H., Vollmer, C. and Nurse, C. A. (2000) Co-release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors. Journal of Physiology, 525, pp. 143–158.Google Scholar
37.Burnstock, G. (2008) The journey to establish purinergic signalling in the gut. Neurogastroenterology and Motility, 20, pp. 8–19.Google Scholar
38.Langley, K. N. and Anderson, H. K. (1895) The innervation of the pelvic and adjoining viscera. Part II. The bladder. Journal of Physiology, 19, pp. 71–84.Google Scholar
39.Burnstock, G., Dumsday, B. and Smythe, A. (1972) Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide. British Journal of Pharmacology, 44, pp. 451–461.Google Scholar
40.Burnstock, G., Cocks, T., Crowe, R. and Kasakov, L. (1978) Purinergic innervation of the guinea-pig urinary bladder. British Journal of Pharmacology, 63, pp. 125–138.Google Scholar
41.Belai, A. and Burnstock, G. (1994) Evidence for coexistence of ATP and nitric oxide in non-adrenergic, non-cholinergic (NANC) inhibitory neurones in the rat ileum, colon and anococcygeus muscle. Cell and Tissue Research, 278, pp. 197–200.Google Scholar
42.Burnstock, G. (2009) Purinergic Cotransmission. Experimental Physiology, 94, pp. 20–24.Google Scholar
43.Kolb, H. A. and Wakelam, M. J. O. (1983) Transmitter-like action of ATP on patched membranes of cultured myoblasts and myotubes. Nature, 303, pp. 621–623.Google Scholar
44.Burnstock, G. (2009) Purinergic cotransmission. ‘Hot Topic’. F1000 Biology Reports, 1, p. 46.Google Scholar
45.Burnstock, G. (2004) Cotransmission. Current Opinion in Pharmacology, 4, pp. 47–52.Google Scholar
46.Bao, J. X., Eriksson, I. E. and Stjärne, L. (1989) Age-related variations in the relative importance of noradrenaline and ATP as mediators of the contractile response of rat tail artery to sympathetic nerve stimulation. Acta Physiolica Scandinavica, 136, pp. 287–288.Google Scholar
47.Palea, S., Artibani, W., Ostardo, E., Trist, D. G. and Pietra, C. (1993) Evidence for purinergic neurotransmission in human urinary bladder affected by interstitial cystitis. Journal of Urology, 150, pp. 2007–2012.Google Scholar
48.Smith, D. J. and Chapple, C. R. (1994) In vitro response of human bladder smooth muscle in unstable obstructed male bladders: a study of pathophysiological causes. Neurourology and Urodynamics, 13, pp. 414–415.Google Scholar
49.Vidal, M., Hicks, P. E. and Langer, S. Z. (1986) Differential effects of α,β-methylene ATP on responses to nerve stimulation in SHR and WKY tail arteries. Naunyn Schmiedeberg's Archives of Pharmacology, 332, pp. 384–390.Google Scholar
50.Bulloch, J. M. and McGrath, J. C. (1992) Evidence for increased purinergic contribution in hypertensive blood vessels exhibiting co-transmission. British Journal of Pharmacology, 107, p. 145P.Google Scholar
51.Burnstock, G. (1996) A unifying purinergic hypothesis for the initiation of pain. Lancet, 347, pp. 1604–1605.Google Scholar
52.Burnstock, G. and Costa, M. (1975) Adrenergic Neurones: Their Organisation, Function and Development in the Peripheral Nervous System (London: Chapman and Hall), pp. 1–225.Google Scholar
53.Burnstock, G. and Verkhratsky, A. (2012) Purinergic Signalling and the Nervous System (Heidelberg/Berlin: Springer), pp. 1–715.Google Scholar
54.Burnstock, G. and Warland, J. J. I. (1987) A pharmacological study of the rabbit saphenous artery in vitro: a vessel with a large purinergic contractile response to sympathetic nerve stimulation. British Journal of Pharmacology, 90, pp. 111–120.Google Scholar
55.Burnstock, G. and Verkhratsky, A. (2010) Vas deferens – a model used to establish sympathetic cotransmission. Trends in Pharmacological Sciences, 31, pp. 131–139.Google Scholar
56.Burnstock, G. and Wong, H. (1978) Comparison of the effects of ultraviolet light and purinergic nerve stimulation on the guinea-pig taenia coli. British Journal of Pharmacology, 62, pp. 293–302.Google Scholar
57.Burnstock, G. (2001) Purinergic signalling in gut. In: M. P. Abbracchio and M. Williams (eds) Handbook of Experimental Pharmacology, Volume 151/II. Purinergic and Pyrimidinergic Signalling II – Cardiovascular, Respiratory, Immune, Metabolic and Gastrointestinal Tract Function (Berlin: Springer-Verlag), pp. 141–238.Google Scholar
58.Burnstock, G. (1977) Autonomic neuroeffector junctions – reflex vasodilatation of the skin. Journal of Investigative Dermatology, 69, pp. 47–57.Google Scholar
59.Burnstock, G. (1996) P2 Purinoceptors: historical perspective and classification. In: D. J. Chadwick and J. A. Goode (eds) P2 Purinoceptors: Localization, Function and Transduction Mechanisms. Ciba Foundation Symposium vol. 198 (Chichester: Wiley), pp. 1–29.Google Scholar
60.Hoyle, C. H. V. (1996) Purinergic cotransmission: parasympathetic and enteric nerves. Seminars in Neuroscience, 8, pp. 207–215.Google Scholar
61.Burnstock, G. (1993) Introduction: Changing face of autonomic and sensory nerves in the circulation. In: L. Edvinsson and R. Uddman (eds) Vascular Innervation and Receptor Mechanisms: New Perspectives (USA: Academic Press), pp. 1–22.Google Scholar
62.Silinsky, E. M. and Hubbard, J. I. (1973) Release of ATP from rat motor nerve terminals. Nature, 243, pp. 404–405.Google Scholar
63.Henning, R. H. (1997) Purinoceptors in neuromuscular transmission. Pharmacology & Therapeutics, 74, pp. 115–128.Google Scholar
64.Richardson, P. J. and Brown, S. J. (1987) ATP release from affinity-purified rat cholinergic nerve terminals. Journal of Neurochemistry, 48, pp. 622–630.Google Scholar
65.Sperlágh, B., Sershen, H., Lajtha, A. and Vizi, E. S. (1998) Co-release of endogenous ATP and [3H]noradrenaline from rat hypothalamic slices: origin and modulation by α 2-adrenoceptors. Neuroscience, 82, pp. 511–520.Google Scholar
66.Poelchen, W., Sieler, D., Wirkner, K. and Illes, P. (2001) Co-transmitter function of ATP in central catecholaminergic neurons of the rat. Neuroscience, 102, pp. 593–602.Google Scholar
67.Jo, Y. H. and Role, L. W. (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. Journal of Neuroscience, 22, pp. 4794–4804.Google Scholar
68.Krügel, U., Schraft, T., Kittner, H., Kiess, W. and Illes, P. (2003) Basal and feeding-evoked dopamine release in the rat nucleus accumbens is depressed by leptin. European Journal of Pharmacology, 482, pp. 185–187.Google Scholar
69.Mori, M., Heuss, C., Gahwiler, B. H. and Gerber, U. (2001) Fast synaptic transmission mediated by P2X receptors in CA3 pyramidal cells of rat hippocampal slice cultures. Journal of Physiology, 535, pp. 115–123.Google Scholar
70.Fujii, S., Sasaki, H., Mikoshiba, K., Kuroda, Y., Yamazaki, Y., Mostafa, T. A. and Kato, H. (2004) A chemical LTP induced by co-activation of metabotropic and N-methyl-D-aspartate glutamate receptors in hippocampal CA1 neurons. Brain Research, 999, pp. 20–28.Google Scholar