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. 1983 Sep;80(1):123–131. doi: 10.1111/j.1476-5381.1983.tb11057.x

Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission.

T Akasu, M Kojima, K Koketsu
PMCID: PMC2044974  PMID: 6197126

Abstract

The effect of substance P on the sensitivity of nicotinic acetylcholine (ACh) receptors of bullfrog sympathetic ganglion cells and frog skeletal muscle endplate was examined electrophysiologically. The amplitude of ACh-induced postsynaptic potential (ACh potential) and current (ACh current) were reversibly and dose-dependently reduced by substance P at low concentrations (0.42-42 microM). The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 microM). Substance P (4.2 microM) shifted the S-shaped dose-response curve of the ACh current downward. A Lineweaver-Burk plot constructed from the dose-response curve revealed that substance P depressed the maximum response (Vmax) without changing the apparent affinity (Km) of ACh for the receptor. Substance P (0.42-42 microM) did not alter the reversal potential of the ACh current of the endplate. The half-decay time of endplate current (e.p.c.) and its voltage-dependency were not altered by substance P in these concentrations. The depression of the ACh current by substance P may not be due to a blockade of the opened channel which has been activated by the preceding combination of ACh with the receptor. These results suggest that substance P suppresses the sensitivity of nicotinic ACh-receptors of the sympathetic ganglion cell and skeletal muscle endplate, acting on a certain allosteric site but not the recognition site of ACh in the receptor-ionic channel complex.

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Selected References

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  1. Adler M., Albuquerque E. X. An analysis of the action of atropine and scopolamine on the end-plate current of frog sartorius muscle. J Pharmacol Exp Ther. 1976 Feb;196(2):360–372. [PubMed] [Google Scholar]
  2. Akasu T., Hirai K., Koketsu K. 5-hydroxytryptamine controls ACh-receptor sensitivity of bullfrog sympathetic ganglion cells. Brain Res. 1981 Apr 27;211(1):217–220. doi: 10.1016/0006-8993(81)90087-1. [DOI] [PubMed] [Google Scholar]
  3. Akasu T., Hirai K., Koketsu K. Increase of acetylcholine-receptor sensitivity by adenosine triphosphate: a novel action of ATP on ACh-sensitivity. Br J Pharmacol. 1981 Oct;74(2):505–507. doi: 10.1111/j.1476-5381.1981.tb09997.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Akasu T., Koketsu K. Voltage-clamp studies of a slow inward current in bullfrog sympathetic ganglion cells. Neurosci Lett. 1981 Nov 4;26(3):259–262. doi: 10.1016/0304-3940(81)90142-7. [DOI] [PubMed] [Google Scholar]
  5. Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BOYD I. A., MARTIN A. R. The end-plate potential in mammalian muscle. J Physiol. 1956 Apr 27;132(1):74–91. doi: 10.1113/jphysiol.1956.sp005503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Dun N. J., Jiang Z. G. Non-cholinergic excitatory transmission in inferior mesenteric ganglia of the guinea-pig: possible mediation by substance P. J Physiol. 1982 Apr;325:145–159. doi: 10.1113/jphysiol.1982.sp014141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Feltz A., Large W. A., Trautmann A. Analysis of atropine action at the frog neutromuscular junction. J Physiol. 1977 Jul;269(1):109–130. doi: 10.1113/jphysiol.1977.sp011895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gage P. W. Generation of end-plate potentials. Physiol Rev. 1976 Jan;56(1):177–247. doi: 10.1152/physrev.1976.56.1.177. [DOI] [PubMed] [Google Scholar]
  12. Jan L. Y., Jan Y. N. Peptidergic transmission in sympathetic ganglia of the frog. J Physiol. 1982 Jun;327:219–246. doi: 10.1113/jphysiol.1982.sp014228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson S. M., Katayama Y., Morita K., North R. A. Mediators of slow synaptic potentials in the myenteric plexus of the guinea-pig ileum. J Physiol. 1981 Nov;320:175–186. doi: 10.1113/jphysiol.1981.sp013942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KOKETSU K., CERF J. A., NISHI S. Effect of quaternary ammonium ions on electrical activity of spinal ganglion cells in frogs. J Neurophysiol. 1959 Mar;22(2):177–194. doi: 10.1152/jn.1959.22.2.177. [DOI] [PubMed] [Google Scholar]
  15. Katayama Y., North R. A. Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature. 1978 Jul 27;274(5669):387–388. doi: 10.1038/274387a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Katz B., Miledi R. The binding of acetylcholine to receptors and its removal from the synaptic cleft. J Physiol. 1973 Jun;231(3):549–574. doi: 10.1113/jphysiol.1973.sp010248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz B., Miledi R. The statistical nature of the acetycholine potential and its molecular components. J Physiol. 1972 Aug;224(3):665–699. doi: 10.1113/jphysiol.1972.sp009918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koketsu K., Akasu T., Miyagawa M., Hirai K. Biogenic antagonists of the nicotinic receptor: their interactions with erabutoxin. Brain Res. 1982 Nov 4;250(2):391–393. doi: 10.1016/0006-8993(82)90438-3. [DOI] [PubMed] [Google Scholar]
  20. Koketsu K., Akasu T., Miyagawa M., Hirai K. Modulation of nicotinic transmission by biogenic amines in bullfrog sympathetic ganglia. J Auton Nerv Syst. 1982 Jul;6(1):47–53. doi: 10.1016/0165-1838(82)90021-2. [DOI] [PubMed] [Google Scholar]
  21. Koketsu K., Miyagawa M., Akasu T. Catecholamine modulates nicotinic ACh-receptor sensitivity. Brain Res. 1982 Mar 25;236(2):487–491. doi: 10.1016/0006-8993(82)90732-6. [DOI] [PubMed] [Google Scholar]
  22. Kuba K., Koketsu K. Synaptic events in sympathetic ganglia. Prog Neurobiol. 1978;11(2):77–169. doi: 10.1016/0301-0082(78)90010-2. [DOI] [PubMed] [Google Scholar]
  23. Kuba K., Nishi S. Characteristics of fast excitatory postsynaptic current in bullfrog sympathetic ganglion cells. Effects of membrane potential, temperature and Ca ions. Pflugers Arch. 1979 Jan 31;378(3):205–212. doi: 10.1007/BF00592737. [DOI] [PubMed] [Google Scholar]
  24. Magleby K. L., Stevens C. F. The effect of voltage on the time course of end-plate currents. J Physiol. 1972 May;223(1):151–171. doi: 10.1113/jphysiol.1972.sp009839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neher E., Sakmann B. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature. 1976 Apr 29;260(5554):799–802. doi: 10.1038/260799a0. [DOI] [PubMed] [Google Scholar]
  26. Neher E., Steinbach J. H. Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol. 1978 Apr;277:153–176. doi: 10.1113/jphysiol.1978.sp012267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ryall R. W., Belcher G. Substance P selectively blocks nicotinic receptors on Renshaw cells: a possible synaptic inhibitory mechanism. Brain Res. 1977 Dec 2;137(2):376–380. doi: 10.1016/0006-8993(77)90350-x. [DOI] [PubMed] [Google Scholar]
  28. Steinbach A. B. A kinetic model for the action of xylocaine on receptors for acetylcholine. J Gen Physiol. 1968 Jul;52(1):162–180. doi: 10.1085/jgp.52.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Steinbach A. B. Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. J Gen Physiol. 1968 Jul;52(1):144–161. doi: 10.1085/jgp.52.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. TAKEUCHI A., TAKEUCHI N. Active phase of frog's end-plate potential. J Neurophysiol. 1959 Jul;22(4):395–411. doi: 10.1152/jn.1959.22.4.395. [DOI] [PubMed] [Google Scholar]

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