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. 1986 Jun;146:1–30.

Autonomic neuromuscular junctions: current developments and future directions.

G Burnstock 1
PMCID: PMC1166521  PMID: 3319994

Abstract

(1) The autonomic neuromuscular junction has been defined, with emphasis on the role of muscle effector bundles and en passage release of transmitter from extensive terminal nerve varicosities to diffuse to muscle across variable and often wide junctional clefts. (2) A multiplicity of neurotransmitters is described in the autonomic nervous system, including purines, peptides, amino acids and monoamines. The ultrastructural identification, projections, roles and interactions of the different nerve types have been discussed. (3) It has been suggested that the part played by peripheral neuroeffector control mechanisms has been underestimated and includes cotransmission, pre- and post-junctional neuromodulation, and the participation of locally released agents. (4) A time-lapse film was shown of the formation of autonomic neuromuscular junctions in culture, introducing questions relating to long-term 'trophic' influences in the autonomic nervous system.

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Selected References

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

  1. Alm P., Alumets J., Brodin E., Håkanson R., Nilsson G., Sjöberg N. O., Sundler F. Peptidergic (substance P) nerves in the genito-urinary tract. Neuroscience. 1978;3(4-5):419–425. doi: 10.1016/0306-4522(78)90044-1. [DOI] [PubMed] [Google Scholar]
  2. Ambache N., Zar M. A. Non-cholinergic transmission by post-ganglionic motor neurones in the mammalian bladder. J Physiol. 1970 Oct;210(3):761–783. doi: 10.1113/jphysiol.1970.sp009240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bałuk P., Jessen K. R., Saffrey M. J., Burnstock G. The enteric nervous system in tissue culture. II. Ultrastructural studies of cell types and their relationships. Brain Res. 1983 Feb 28;262(1):37–47. doi: 10.1016/0006-8993(83)90467-5. [DOI] [PubMed] [Google Scholar]
  4. Buckley N. J., Burnstock G. Distribution of muscarinic receptors on cultured myenteric neurons. Brain Res. 1984 Sep 17;310(1):133–137. doi: 10.1016/0006-8993(84)90016-7. [DOI] [PubMed] [Google Scholar]
  5. Buckley N., Burnstock G. Autoradiographic localisation of muscarinic receptors in guinea-pig intestine: distribution of high and low affinity agonist binding sites. Brain Res. 1984 Feb 27;294(1):15–22. doi: 10.1016/0006-8993(84)91305-2. [DOI] [PubMed] [Google Scholar]
  6. Burnstock G. Autonomic neuroeffector junctions--reflex vasodilatation of the skin. J Invest Dermatol. 1977 Jul;69(1):47–57. doi: 10.1111/1523-1747.ep12497872. [DOI] [PubMed] [Google Scholar]
  7. Burnstock G., Cocks T., Crowe R., Kasakov L. Purinergic innervation of the guinea-pig urinary bladder. Br J Pharmacol. 1978 May;63(1):125–138. doi: 10.1111/j.1476-5381.1978.tb07782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burnstock G., Crowe R., Wong H. K. Comparative pharmacological and histochemical evidence for purinergic inhibitory innervation of the portal vein of the rabbit, but not guinea-pig. Br J Pharmacol. 1979 Mar;65(3):377–388. doi: 10.1111/j.1476-5381.1979.tb07841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burnstock G. Do some nerve cells release more than one transmitter? Neuroscience. 1976 Aug;1(4):239–248. doi: 10.1016/0306-4522(76)90054-3. [DOI] [PubMed] [Google Scholar]
  10. Burnstock G., Dumsday B., Smythe A. Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide. Br J Pharmacol. 1972 Mar;44(3):451–461. doi: 10.1111/j.1476-5381.1972.tb07283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Burnstock G. Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacol Rev. 1969 Dec;21(4):247–324. [PubMed] [Google Scholar]
  12. Burnstock G., Griffith S. G., Sneddon P. Autonomic nerves in the precapillary vessel wall. J Cardiovasc Pharmacol. 1984;6 (Suppl 2):S344–S353. doi: 10.1097/00005344-198406002-00009. [DOI] [PubMed] [Google Scholar]
  13. Burnstock G., Hökfelt T., Gershon M. D., Iversen L. L., Kosterlitz H. W., Szurszewski J. H. Non-adrenergic, non-cholinergic autonomic neurotransmission mechanisms. Neurosci Res Program Bull. 1979 Jun;17(3):377–519. [PubMed] [Google Scholar]
  14. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  15. Burnstock G. Review lecture. Neurotransmitters and trophic factors in the autonomic nervous system. J Physiol. 1981;313:1–35. doi: 10.1113/jphysiol.1981.sp013648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Burnstock G. The changing face of autonomic neurotransmission. Acta Physiol Scand. 1986 Jan;126(1):67–91. doi: 10.1111/j.1748-1716.1986.tb07790.x. [DOI] [PubMed] [Google Scholar]
  17. Campbell G. R., Uehara Y., Mark G., Burnstock G. Fine structure of smooth muscle cells grown in tissue culture. J Cell Biol. 1971 Apr;49(1):21–34. doi: 10.1083/jcb.49.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cook R. D., Burnstock G. The altrastructure of Auerbach's plexus in the guinea-pig. I. Neuronal elements. J Neurocytol. 1976 Apr;5(2):171–194. doi: 10.1007/BF01181655. [DOI] [PubMed] [Google Scholar]
  19. Costa M., Furness J. B. The origins, pathways and terminations of neurons with VIP-like immunoreactivity in the guinea-pig small intestine. Neuroscience. 1983 Apr;8(4):665–676. doi: 10.1016/0306-4522(83)90002-7. [DOI] [PubMed] [Google Scholar]
  20. Crowe R., Burnstock G. Fluorescent histochemical localisation of quinacrine-positive neurones in the guinea-pig and rabbit atrium. Cardiovasc Res. 1982 Jul;16(7):384–390. doi: 10.1093/cvr/16.7.384. [DOI] [PubMed] [Google Scholar]
  21. Crowe R., Lincoln J., Blacklay P. F., Pryor J. P., Lumley J. S., Burnstock G. Vasoactive intestinal polypeptide-like immunoreactive nerves in diabetic penis. A comparison between streptozotocin-treated rats and man. Diabetes. 1983 Nov;32(11):1075–1077. doi: 10.2337/diab.32.11.1075. [DOI] [PubMed] [Google Scholar]
  22. Edwards A. V., Bloom S. R. Recent physiological studies of the alimentary autonomic innervation. Scand J Gastroenterol Suppl. 1982;71:77–89. [PubMed] [Google Scholar]
  23. Fujiwara T., Uehara Y. The cytoarchitecture of the wall and the innervation pattern of the microvessels in the rat mammary gland: a scanning electron microscopic observation. Am J Anat. 1984 May;170(1):39–54. doi: 10.1002/aja.1001700104. [DOI] [PubMed] [Google Scholar]
  24. Furness J. B., Campbell G. R., Gillard S. M., Malmfors T., Cobb J. L., Burnstock G. Cellular studies of sympathetic denervation produced by 6-hydroxydopamine in the vas deferens. J Pharmacol Exp Ther. 1970 Jul;174(1):111–122. [PubMed] [Google Scholar]
  25. Furness J. B., Costa M., Miller R. J. Distribution and projections of nerves with enkephalin-like immunoreactivity in the guinea-pig small intestine. Neuroscience. 1983 Apr;8(4):653–664. doi: 10.1016/0306-4522(83)90001-5. [DOI] [PubMed] [Google Scholar]
  26. Furness J. B., Costa M. Neurons with 5-hydroxytryptamine-like immunoreactivity in the enteric nervous system: their projections in the guinea-pig small intestine. Neuroscience. 1982 Feb;7(2):341–349. doi: 10.1016/0306-4522(82)90271-8. [DOI] [PubMed] [Google Scholar]
  27. Furness J. B., Costa M. Types of nerves in the enteric nervous system. Neuroscience. 1980;5(1):1–20. doi: 10.1016/0306-4522(80)90067-6. [DOI] [PubMed] [Google Scholar]
  28. Fyffe R. E., Perl E. R. Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin? Proc Natl Acad Sci U S A. 1984 Nov;81(21):6890–6893. doi: 10.1073/pnas.81.21.6890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gabella G. Innervation of the gastrointestinal tract. Int Rev Cytol. 1979;59:129–193. doi: 10.1016/s0074-7696(08)61662-9. [DOI] [PubMed] [Google Scholar]
  30. Gamse R., Holzer P., Lembeck F. Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br J Pharmacol. 1980 Feb;68(2):207–213. doi: 10.1111/j.1476-5381.1980.tb10409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Gershon M. D. The enteric nervous system. Annu Rev Neurosci. 1981;4:227–272. doi: 10.1146/annurev.ne.04.030181.001303. [DOI] [PubMed] [Google Scholar]
  32. Gibbins I. L. Lack of correlation between ultrastructural and pharmacological types of non-adrenergic autonomic nerves. Cell Tissue Res. 1982;221(3):551–581. doi: 10.1007/BF00215701. [DOI] [PubMed] [Google Scholar]
  33. Griffith S. G., Lincoln J., Burnstock G. Serotonin as a neurotransmitter in cerebral arteries. Brain Res. 1982 Sep 16;247(2):388–392. doi: 10.1016/0006-8993(82)91266-5. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Hanani M., Baluk P., Burnstock G. Myenteric neurons express electrophysiological and morphological diversity in tissue culture. J Auton Nerv Syst. 1982 Mar;5(2):155–164. doi: 10.1016/0165-1838(82)90036-4. [DOI] [PubMed] [Google Scholar]
  36. Hanani M., Burnstock G. Substance P evokes slow and fast responses in cultured myenteric neurons of the guinea pig. Neurosci Lett. 1984 Jul 13;48(1):19–23. doi: 10.1016/0304-3940(84)90282-9. [DOI] [PubMed] [Google Scholar]
  37. Hanani M., Burnstock G. The actions of substance P and serotonin on myenteric neurons in tissue culture. Brain Res. 1985 Dec 9;358(1-2):276–281. doi: 10.1016/0006-8993(85)90971-0. [DOI] [PubMed] [Google Scholar]
  38. Hassall C. J., Burnstock G. Neuropeptide Y-like immunoreactivity in cultured intrinsic neurones of the heart. Neurosci Lett. 1984 Nov 23;52(1-2):111–115. doi: 10.1016/0304-3940(84)90359-8. [DOI] [PubMed] [Google Scholar]
  39. Hills J., Meldrum L. A., Klarskov P., Burnstock G. A novel non-adrenergic, non-cholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. Eur J Pharmacol. 1984 Apr 6;99(4):287–293. doi: 10.1016/0014-2999(84)90135-3. [DOI] [PubMed] [Google Scholar]
  40. Hägermark O., Hökfelt T., Pernow B. Flare and itch induced by substance P in human skin. J Invest Dermatol. 1978 Oct;71(4):233–235. doi: 10.1111/1523-1747.ep12515092. [DOI] [PubMed] [Google Scholar]
  41. Hökfelt T., Elfvin L. G., Elde R., Schultzberg M., Goldstein M., Luft R. Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3587–3591. doi: 10.1073/pnas.74.8.3587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Hökfelt T., Schultzberg M., Elde R., Nilsson G., Terenius L., Said S., Goldstein M. Peptide neurons in peripheral tissues including the urinary tract: immunohistochemical studies. Acta Pharmacol Toxicol (Copenh) 1978;43 (Suppl 2):79–89. doi: 10.1111/j.1600-0773.1978.tb03224.x. [DOI] [PubMed] [Google Scholar]
  43. Jahr C. E., Jessell T. M. ATP excites a subpopulation of rat dorsal horn neurones. Nature. 1983 Aug 25;304(5928):730–733. doi: 10.1038/304730a0. [DOI] [PubMed] [Google Scholar]
  44. Jessen K. R., McConnell J. D., Purves R. D., Burnstock G., Chamley-Campbell J. Tissue culture of mammalian enteric neurons. Brain Res. 1978 Sep 8;152(3):573–579. doi: 10.1016/0006-8993(78)91112-5. [DOI] [PubMed] [Google Scholar]
  45. Jessen K. R., Mirsky R., Dennison M. E., Burnstock G. GABA may be a neurotransmitter in the vertebrate peripheral nervous system. Nature. 1979 Sep 6;281(5726):71–74. doi: 10.1038/281071a0. [DOI] [PubMed] [Google Scholar]
  46. Jessen K. R., Saffrey M. J., Bałuk P., Hanani M., Burnstock G. The enteric nervous system in tissue culture. III. Studies on neuronal survival and the retention of biochemical and morphological differentiation. Brain Res. 1983 Feb 28;262(1):49–62. doi: 10.1016/0006-8993(83)90468-7. [DOI] [PubMed] [Google Scholar]
  47. Jessen K. R., Saffrey M. J., Burnstock G. The enteric nervous system in tissue culture. I. Cell types and their interactions in explants of the myenteric and submucous plexuses from guinea pig, rabbit and rat. Brain Res. 1983 Feb 28;262(1):17–35. doi: 10.1016/0006-8993(83)90466-3. [DOI] [PubMed] [Google Scholar]
  48. Komuro T., Baluk P., Burnstock G. An ultrastructural study of nerve profiles in the myenteric plexus of the rabbit colon. Neuroscience. 1982 Jan;7(1):295–305. doi: 10.1016/0306-4522(82)90167-1. [DOI] [PubMed] [Google Scholar]
  49. Komuro T., Bałuk P., Burnstock G. An ultrastructural study of neurons and non-neuronal cells in the myenteric plexus of the rabbit colon. Neuroscience. 1982 Jul;7(7):1797–1806. doi: 10.1016/0306-4522(82)90037-9. [DOI] [PubMed] [Google Scholar]
  50. Kubo T., Su C. Effects of adenosine on [3H]norepinephrine release from perfused mesenteric arteries of SHR and renal hypertensive rats. Eur J Pharmacol. 1983 Feb 18;87(2-3):349–352. doi: 10.1016/0014-2999(83)90352-7. [DOI] [PubMed] [Google Scholar]
  51. Larsson L. I. Ultrastructural localization of a new neuronal peptide (VIP). Histochemistry. 1977 Oct 22;54(2):173–176. doi: 10.1007/BF00489676. [DOI] [PubMed] [Google Scholar]
  52. Legay C., Saffrey M. J., Burnstock G. Coexistence of immunoreactive substance P and serotonin in neurones of the gut. Brain Res. 1984 Jun 8;302(2):379–382. doi: 10.1016/0006-8993(84)90253-1. [DOI] [PubMed] [Google Scholar]
  53. Loesch A., Burnstock G. Ultrastructural identification of VIP-containing nerve fibres in the myenteric plexus of the rat ileum. J Neurocytol. 1985 Apr;14(2):327–335. doi: 10.1007/BF01258456. [DOI] [PubMed] [Google Scholar]
  54. Lundberg J. M., Hökfelt T., Anggård A., Terenius L., Elde R., Markey K., Goldstein M., Kimmel J. Organizational principles in the peripheral sympathetic nervous system: subdivision by coexisting peptides (somatostatin-, avian pancreatic polypeptide-, and vasoactive intestinal polypeptide-like immunoreactive materials). Proc Natl Acad Sci U S A. 1982 Feb;79(4):1303–1307. doi: 10.1073/pnas.79.4.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Lundberg J. M., Terenius L., Hökfelt T., Martling C. R., Tatemoto K., Mutt V., Polak J., Bloom S., Goldstein M. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand. 1982 Dec;116(4):477–480. doi: 10.1111/j.1748-1716.1982.tb07171.x. [DOI] [PubMed] [Google Scholar]
  56. Mackenzie I., Burnstock G. Neuropeptide action on the guinea-pig bladder; a comparison with the effects of field stimulation and ATP. Eur J Pharmacol. 1984 Oct 1;105(1-2):85–94. doi: 10.1016/0014-2999(84)90651-4. [DOI] [PubMed] [Google Scholar]
  57. Merrillees N. C. The nervous environment of individual smooth muscle cells of the guinea pig vas deferens. J Cell Biol. 1968 Jun;37(3):794–817. doi: 10.1083/jcb.37.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. North R. A. Electrophysiology of the enteric nervous system. Neuroscience. 1982 Feb;7(2):315–325. doi: 10.1016/0306-4522(82)90269-x. [DOI] [PubMed] [Google Scholar]
  59. Olson L., Alund M., Norberg K. A. Fluorescence-microscopical demonstration of a population of gastro-intestinal nerve fibres with a selective affinity for quinacrine. Cell Tissue Res. 1976 Sep 1;171(4):407–423. doi: 10.1007/BF00220234. [DOI] [PubMed] [Google Scholar]
  60. Polak J. M., Buchan A. M., Probert L., Tapia F., de Mey J., Bloom S. R. Regulatory peptides in endocrine cells and autonomic nerves: electron immunocytochemistry. Scand J Gastroenterol Suppl. 1981;70:11–23. [PubMed] [Google Scholar]
  61. Potter D. D., Furshpan E. J., Landis S. C. Transmitter status in cultured rat sympathetic neurons: plasticity and multiple function. Fed Proc. 1983 Apr;42(6):1626–1632. [PubMed] [Google Scholar]
  62. Rogers D. C., Burnstock G. The interstitial cell and its place in the concept of the autonomic ground plexus. J Comp Neurol. 1966 Feb;126(2):255–284. doi: 10.1002/cne.901260207. [DOI] [PubMed] [Google Scholar]
  63. Saffrey M. J., Legay C., Burnstock G. Development of 5-hydroxytryptamine-like immunoreactive neurones in cultures of the myenteric plexus from the guinea-pig caecum. Brain Res. 1984 Jun 18;304(1):105–116. doi: 10.1016/0006-8993(84)90865-5. [DOI] [PubMed] [Google Scholar]
  64. Schultzberg M., Hökfelt T., Terenius L., Elfvin L. G., Lundberg J. M., Brandt J., Elde R. P., Goldstein M. Enkephalin immunoreactive nerve fibres and cell bodies in sympathetic ganglia of the guinea-pig and rat. Neuroscience. 1979;4(2):249–270. doi: 10.1016/0306-4522(79)90087-3. [DOI] [PubMed] [Google Scholar]
  65. Sneddon P., Burnstock G. Inhibition of excitatory junction potentials in guinea-pig vas deferens by alpha, beta-methylene-ATP: further evidence for ATP and noradrenaline as cotransmitters. Eur J Pharmacol. 1984 Apr 13;100(1):85–90. doi: 10.1016/0014-2999(84)90318-2. [DOI] [PubMed] [Google Scholar]
  66. Sneddon P., Westfall D. P. Pharmacological evidence that adenosine triphosphate and noradrenaline are co-transmitters in the guinea-pig vas deferens. J Physiol. 1984 Feb;347:561–580. doi: 10.1113/jphysiol.1984.sp015083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Uehara Y., Burnstock G. Demonstration of "gap junctions" between smooth muscle cells. J Cell Biol. 1970 Jan;44(1):215–217. doi: 10.1083/jcb.44.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Uehara Y., Fujiwara T., Komuro T. [Fine structure of the myenteric plexus of Auerbach, studied by scanning and transmission electron microscopy (author's transl)]. Nihon Heikatsukin Gakkai Zasshi. 1981 Sep;17(3):81–91. [PubMed] [Google Scholar]
  69. Wood J. D. Enteric neurophysiology. Am J Physiol. 1984 Dec;247(6 Pt 1):G585–G598. doi: 10.1152/ajpgi.1984.247.6.G585. [DOI] [PubMed] [Google Scholar]
  70. Young W. S., 3rd, Kuhar M. J. A new method for receptor autoradiography: [3H]opioid receptors in rat brain. Brain Res. 1979 Dec 28;179(2):255–270. doi: 10.1016/0006-8993(79)90442-6. [DOI] [PubMed] [Google Scholar]

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