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. 1982;323:543–567. doi: 10.1113/jphysiol.1982.sp014091

5-Hydroxytryptamine receptors of visceral primary afferent neurones on rabbit nodose ganglia

H Higashi 1, S Nishi 1
PMCID: PMC1250375  PMID: 7097585

Abstract

1. The electrophysiological characteristics of 5-hydroxytryptamine (5-HT) receptors distributed on visceral primary afferent neurones (the nodose ganglion cells of the vagus) in rabbits were investigated with intracellular recording and voltage-clamp techniques.

2. In response to 5-HT applied by superfusion (≥ 10 μm) or by ionophoresis (≥ 5 nA, 50 msec), the majority of type C neurones (mean axonal conduction velocity: 0·83±0·25 m/sec) showed a rapid depolarization of 20-30 mV in amplitude which was followed by a hyperpolarization of a few millivolts. Both the initial depolarization and afterhyperpolarization were associated with a reduction in membrane resistance.

3. Type A neurones (mean axonal conduction velocity: 7·7±0·4 m/sec) did not show any significant alterations in membrane potential and resistance during or after application of 5-HT.

4. The initial depolarization induced by 5-HT was abolished by Na+-free Krebs solution and showed a reduction of a few millivolts in K+-free or Ca2+-free Krebs solution. The response in normal Krebs solution was reversed at a membrane potential level of +7·3±1·1 mV.

5. The afterhyperpolarization disappeared in Na+-free or Ca2+-free Krebs solution, while it was markedly enhanced in K+-free Krebs solution. The response in normal Krebs solution reversed at a membrane potential of -88·7±0·8 mV, and was abolished at membrane potentials more positive than -20 mV.

6. Unlike 5-HT voltage responses, which were biphasic in the majority of neurones examined, 5-HT induced currents were usually monophasic when recorded at holding membrane levels ranging from -80 to +50 mV. The reversal potential of the inward current was +7·5±0·8 mV which was in good agreement with the reversal level for 5-HT-induced depolarizations. The reversal potentials for inward currents which were obtained at various concentrations of Na+ or K+ corresponded to the theoretical values calculated by the equivalent circuit equation.

7. These results suggest that the initial depolarization induced by 5-HT is due mainly to simultaneous increases in Na+ and K+ conductances, while the afterhyperpolarization is brought about by an increase of K+ conductance which is triggered by a voltage-dependent influx of Na+ and Ca2+.

8. The mean value for the `limiting slope' of conductance change vs. 5-HT concentration and the slope of 5-HT current vs. 5-HT concentration obtained by superfusion of 5-HT, were in good agreement, 1·84±0·26 and 1·88±0·31, respectively. On the other hand, the mean Hill coefficient obtained from the dose—response curves for the inward current induced by ionophoresis was 2·51±0·14.

9. Tetrodotoxin (0·2 μm) blocked the soma action potential completely, but did not show any effect on 5-HT-induced responses.

10. (+)-Lysergic acid diethylamide and methysergide (1-100 μm) had no depressant effect on the 5-HT-induced depolarization.

11. (+)-Tubocurarine at low concentrations (1-5 μm) inhibited the 5-HT induced inward current competitively. The mode of its inhibitory action became noncompetitive at higher concentrations (10-20 μm).

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Selected References

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  1. AGOSTONI E., CHINNOCK J. E., DE DALY M. B., MURRAY J. G. Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J Physiol. 1957 Jan 23;135(1):182–205. doi: 10.1113/jphysiol.1957.sp005703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R. An analysis of the dose-response curve at voltage-clamped frog-endplates. Pflugers Arch. 1975 Oct 28;360(2):145–153. doi: 10.1007/BF00580537. [DOI] [PubMed] [Google Scholar]
  3. Ascher P., Large W. A., Rang H. P. Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells. J Physiol. 1979 Oct;295:139–170. doi: 10.1113/jphysiol.1979.sp012958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BULBRING E., LIN R. C. The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity. J Physiol. 1958 Mar 11;140(3):381–407. [PMC free article] [PubMed] [Google Scholar]
  5. Beck P. W., Handwerker H. O. Bradykinin and serotonin effects on various types of cutaneous nerve fibers. Pflugers Arch. 1974 Mar 11;347(3):209–222. doi: 10.1007/BF00592598. [DOI] [PubMed] [Google Scholar]
  6. Colquhoun D., Dreyer F., Sheridan R. E. The actions of tubocurarine at the frog neuromuscular junction. J Physiol. 1979 Aug;293:247–284. doi: 10.1113/jphysiol.1979.sp012888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Costa M., Furness J. B. The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br J Pharmacol. 1979 Feb;65(2):237–248. doi: 10.1111/j.1476-5381.1979.tb07824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DOUGLAS W. W., RITCHIE J. M. On excitation of non-medullated afferent fibres in the vagus and aortic nerves by pharmacological agents. J Physiol. 1957 Aug 29;138(1):31–43. doi: 10.1113/jphysiol.1957.sp005836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Groat W. C., Lalley P. M. Interaction between picrotoxin and 5-hydroxytryptamine in the superior cervical ganglion of the cat. Br J Pharmacol. 1973 Jun;48(2):233–244. doi: 10.1111/j.1476-5381.1973.tb06909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Deschenes M., Feltz P., Lamour Y. A model for an estimate in vivo of the ionic basis of presynaptic inhibition: an intracellular analysis of the GABA-induced depolarization in rat dorsal root ganglia. Brain Res. 1976 Dec 24;118(3):486–493. doi: 10.1016/0006-8993(76)90318-8. [DOI] [PubMed] [Google Scholar]
  11. Dreyer F., Peper K. Density and dose-response curve of acetylcholine receptors in frog neuromuscular junction. Nature. 1975 Feb 20;253(5493):641–643. doi: 10.1038/253641a0. [DOI] [PubMed] [Google Scholar]
  12. Dreyer F., Peper K., Sterz R. Determination of dose-response curves by quantitative ionophoresis at the frog neuromuscular junction. J Physiol. 1978 Aug;281:395–419. doi: 10.1113/jphysiol.1978.sp012430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dunin-Barkovskii V. L., Kovalev S. A., Magazanik L. G., Potapova T. V., Chailakhian L. M. Potentsialy ravnovesiia postsinapticheskoi membrany, aktivirovannoi razlichnymi kholinomineikami, pri izmenenii vnekletochnoi ionnoi sredy. Biofizika. 1969 May-Jun;14(3):485–494. [PubMed] [Google Scholar]
  14. FELDBERG W., TOH C. C. Distribution of 5-hydroxytryptamine (serotonin, enteramine) in the wall of the digestive tract. J Physiol. 1953 Feb 27;119(2-3):352–362. doi: 10.1113/jphysiol.1953.sp004850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. FJALLBRANT N., IGGO A. The effect of histamine, 5-hydroxytryptamine and acetylcholine on cutaneous afferent fibres. J Physiol. 1961 May;156:578–590. doi: 10.1113/jphysiol.1961.sp006694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feltz A., Mallart A. Ionic permeability changes induced by some cholinergic agonists on normal and denervated frog muscles. J Physiol. 1971 Oct;218(1):101–116. doi: 10.1113/jphysiol.1971.sp009606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Feltz P., Rasminsky M. A model for the mode of action of GABA on primary afferent terminals: depolarizing effects of GABA applied iontophoretically to neurones of mammalian dorsal root ganglia. Neuropharmacology. 1974 Jun;13(6):553–563. doi: 10.1016/0028-3908(74)90145-2. [DOI] [PubMed] [Google Scholar]
  18. Fock S., Mense S. Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin. Brain Res. 1976 Apr 9;105(3):459–469. doi: 10.1016/0006-8993(76)90593-x. [DOI] [PubMed] [Google Scholar]
  19. Foreman R. D., Schmidt R. F., Willis W. D. Effects of mechanical and chemical stimulation of fine muscle afferents upon primate spinothalamic tract cells. J Physiol. 1979 Jan;286:215–231. doi: 10.1113/jphysiol.1979.sp012615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fuller R. W. Pharmacology of central serotonin neurons. Annu Rev Pharmacol Toxicol. 1980;20:111–127. doi: 10.1146/annurev.pa.20.040180.000551. [DOI] [PubMed] [Google Scholar]
  21. GADDUM J. H., PICARELLI Z. P. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 1957 Sep;12(3):323–328. doi: 10.1111/j.1476-5381.1957.tb00142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gallego R., Eyzaguirre C. Membrane and action potential characteristics of A and C nodose ganglion cells studied in whole ganglia and in tissue slices. J Neurophysiol. 1978 Sep;41(5):1217–1232. doi: 10.1152/jn.1978.41.5.1217. [DOI] [PubMed] [Google Scholar]
  23. Gerschenfeld H. M., Paupardin-Tritsch D. Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine. J Physiol. 1974 Dec;243(2):427–456. doi: 10.1113/jphysiol.1974.sp010761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gerschenfeld H. M., Paupardin-Tritsch D. On the transmitter function of 5-hydroxytryptamine at excitatory and inhibitory monosynaptic junctions. J Physiol. 1974 Dec;243(2):457–481. doi: 10.1113/jphysiol.1974.sp010762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gerschenfeld H. M., Stefani E. An electrophysiological study of 5-hydroxytryptamine receptors of neurones in the molluscan nervous system. J Physiol. 1966 Aug;185(3):684–700. doi: 10.1113/jphysiol.1966.sp008010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ginsborg B. L., Kado R. T. Voltage-current relationship of a carbachol-induced potassium-ion pathway in Aplysia neurones. J Physiol. 1975 Mar;245(3):713–725. doi: 10.1113/jphysiol.1975.sp010870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Grossman Y., Spira M. E., Parnas I. Differential flow of information into branches of a single axon. Brain Res. 1973 Dec 21;64:379–386. doi: 10.1016/0006-8993(73)90191-1. [DOI] [PubMed] [Google Scholar]
  28. HODGKIN A. L., HOROWICZ P. The influence of potassium and chloride ions on the membrane potential of single muscle fibres. J Physiol. 1959 Oct;148:127–160. doi: 10.1113/jphysiol.1959.sp006278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Haefely W. The effects of 5-hydroxytryptamine and some related compounds on the cat superior cervical ganglion in situ. Naunyn Schmiedebergs Arch Pharmacol. 1974;281(2):145–165. doi: 10.1007/BF00503495. [DOI] [PubMed] [Google Scholar]
  31. Haigler H. J., Aghajanian G. K. Serotonin receptors in the brain. Fed Proc. 1977 Jul;36(8):2159–2164. [PubMed] [Google Scholar]
  32. Hartzell H. C., Kuffler S. W., Yoshikami D. Post-synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse. J Physiol. 1975 Oct;251(2):427–463. doi: 10.1113/jphysiol.1975.sp011102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Higashi H. 5-hydroxytryptamine receptors on visceral primary afferent neurones in the nodose ganglion of the rabbit. Nature. 1977 Jun 2;267(5610):448–450. doi: 10.1038/267448a0. [DOI] [PubMed] [Google Scholar]
  34. Hirst G. D., Silinsky E. M. Some effects of 5-hydroxytryptamine, dopamine and noradrenaline on neurones in the submucous plexus of guinea-pig small intestine. J Physiol. 1975 Oct;251(3):817–832. doi: 10.1113/jphysiol.1975.sp011124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Hong S. K., Kniffke K. D., Mense S., Schmidt R. F., Wendisch M. Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents. J Physiol. 1979 May;290(2):129–140. doi: 10.1113/jphysiol.1979.sp012764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Jacobs L., Comroe J. H., Jr Reflex apnea, bradycardia, and hypotension produced by serotonin and phenyldiguanide acting on the nodose ganglia of the cat. Circ Res. 1971 Aug;29(2):145–155. doi: 10.1161/01.res.29.2.145. [DOI] [PubMed] [Google Scholar]
  37. Jaffe R. A., Sampson S. R. Analysis of passive and active electrophysiologic properties of neurons in mammalian nodose ganglia maintained in vitro. J Neurophysiol. 1976 Jul;39(4):802–815. doi: 10.1152/jn.1976.39.4.802. [DOI] [PubMed] [Google Scholar]
  38. Johnson S. M., Katayama Y., North R. A. Multiple actions of 5-hydroxytryptamine on myenteric neurones of the guinea-pig ileum. J Physiol. 1980 Jul;304:459–470. doi: 10.1113/jphysiol.1980.sp013336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Jordan L. M., Frederickson R. C., Phillis J. W., Lake N. Microelectrophoresis of 5-hydroxytryptamine: a clarification of its action on cerebral cortical neurones. Brain Res. 1972 May 26;40(2):552–558. doi: 10.1016/0006-8993(72)90161-8. [DOI] [PubMed] [Google Scholar]
  40. Katz B., Miledi R. A re-examination of curare action at the motor endplate. Proc R Soc Lond B Biol Sci. 1978 Dec 4;203(1151):119–133. doi: 10.1098/rspb.1978.0096. [DOI] [PubMed] [Google Scholar]
  41. Katz B., Miledi R. Tetrodotoxin and neuromuscular transmission. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):8–22. doi: 10.1098/rspb.1967.0010. [DOI] [PubMed] [Google Scholar]
  42. Koketsu K. Cholinergic synaptic potentials and the underlying ionic mechasims. Fed Proc. 1969 Jan-Feb;28(1):101–112. [PubMed] [Google Scholar]
  43. Linder T. M., Quastel D. M. A voltage-clamp study of the permeability change induced by quanta of transmitter at the mouse end-plate. J Physiol. 1978 Aug;281:535–558. doi: 10.1113/jphysiol.1978.sp012438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Machová J., Boska D. The effect of 5-hydroxytryptamine, dimethylphenylpiperazinium and acetylcholine on transmission and surface potential in the cat sympathetic ganglion. Eur J Pharmacol. 1969 Aug;7(2):152–158. doi: 10.1016/0014-2999(69)90004-1. [DOI] [PubMed] [Google Scholar]
  45. Mense S. Nervous outflow from skeletal muscle following chemical noxious stimulation. J Physiol. 1977 May;267(1):75–88. doi: 10.1113/jphysiol.1977.sp011802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Mense S., Schmidt R. F. Activation of group IV afferent units from muscle by algesic agents. Brain Res. 1974 Jun 7;72(2):305–310. doi: 10.1016/0006-8993(74)90870-1. [DOI] [PubMed] [Google Scholar]
  47. Nishi K. The action of 5-hydroxytryptamine on chemoreceptor discharges of the cat's carotid body. Br J Pharmacol. 1975 Sep;55(1):27–40. doi: 10.1111/j.1476-5381.1975.tb07606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Nishi S., Minota S., Karczmar A. G. Primary afferent neurones: the ionic mechanism of GABA-mediated depolarization. Neuropharmacology. 1974 Mar;13(3):215–219. doi: 10.1016/0028-3908(74)90110-5. [DOI] [PubMed] [Google Scholar]
  49. Nistri A., Constanti A. Pharmacological characterization of different types of GABA and glutamate receptors in vertebrates and invertebrates. Prog Neurobiol. 1979;13(2):117–235. doi: 10.1016/0301-0082(79)90016-9. [DOI] [PubMed] [Google Scholar]
  50. PAINTAL A. S. EFFECTS OF DRUGS ON VERTEBRATE MECHANORECEPTORS. Pharmacol Rev. 1964 Dec;16:341–380. [PubMed] [Google Scholar]
  51. Rang H. P. Acetylcholine receptors. Q Rev Biophys. 1974 Jul;7(3):283–399. doi: 10.1017/s0033583500001463. [DOI] [PubMed] [Google Scholar]
  52. Riccioppo Neto F. The depolarizing action of 5-HT on mammalian non-myelinated nerve fibres. Eur J Pharmacol. 1978 Jun 15;49(4):351–356. doi: 10.1016/0014-2999(78)90308-4. [DOI] [PubMed] [Google Scholar]
  53. Ritchie A. K., Fambrough D. M. Ionic properties of the acetylcholine receptor in cultured rat myotubes. J Gen Physiol. 1975 Jun;65(6):751–767. doi: 10.1085/jgp.65.6.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. TAKEUCHI A., TAKEUCHI N. On the permeability of end-plate membrane during the action of transmitter. J Physiol. 1960 Nov;154:52–67. doi: 10.1113/jphysiol.1960.sp006564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. TAKEUCHI N. Effects of calcium on the conductance change of the end-plate membrane during the action of transmitter. J Physiol. 1963 Jun;167:141–155. doi: 10.1113/jphysiol.1963.sp007137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wallis D. I., North R. A. The action of 5-hydroxytryptamine on single neurones of the rabbit superior cervical ganglion. Neuropharmacology. 1978 Dec;17(12):1023–1028. doi: 10.1016/0028-3908(78)90028-x. [DOI] [PubMed] [Google Scholar]
  57. Wallis D. I., Woodward B. Membrane potential changes induced by 5-hydroxytryptamine in the rabbit superior cervical ganglion. Br J Pharmacol. 1975 Oct;55(2):199–212. doi: 10.1111/j.1476-5381.1975.tb07629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Watanabe S., Koketsu K. 5-HT hyperpolarization of bullfrog sympathetic ganglion cell membrane. Experientia. 1973 Nov 15;29(11):1370–1372. doi: 10.1007/BF01922825. [DOI] [PubMed] [Google Scholar]
  59. Werman R. An electrophysiological approach to drug-receptor mechanisms. Comp Biochem Physiol. 1969 Sep 15;30(6):997–1017. doi: 10.1016/0010-406x(69)91038-x. [DOI] [PubMed] [Google Scholar]
  60. Westfall T. C. Local regulation of adrenergic neurotransmission. Physiol Rev. 1977 Oct;57(4):659–728. doi: 10.1152/physrev.1977.57.4.659. [DOI] [PubMed] [Google Scholar]
  61. Wood J. D., Mayer C. J. Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol. 1979 Mar;42(2):582–593. doi: 10.1152/jn.1979.42.2.582. [DOI] [PubMed] [Google Scholar]

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