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. 1980 Dec;77(12):7458–7462. doi: 10.1073/pnas.77.12.7458

[3H]Phencyclidine: a probe for the ionic channel of the nicotinic receptor.

M E Eldefrawi, A T Eldefrawi, R S Aronstam, M A Maleque, J E Warnick, E X Albuquerque
PMCID: PMC350523  PMID: 6261260

Abstract

To evaluate [3H]phencyclidine ([3H]PCP)as a probe for the ionic channel of the nicotinic receptor, the characteristics of its binding to electric organ membranes od Torpedo ocellata and its effects on frog sartorius muscle were studied. Similar to PCP, [3H]PCP depressed the peak amplitude of endplate current, caused nonlinearity in the voltage-current relationship at negative potentials, accelerated the decay time of the end-plate current, and shortened the channel lifetime. Thus, [3H]PCP interacted with the ionic channel of the nicotinic receptor, although there were a few differences between its effect and that of PCP. Binding of [3H]PCP to Torpedo membranes was to sites on the ionic channel of acetylcholine (AcCho) receptor because it was saturable, dependent upon protein concentration, and inhibited by drugs that interact with the ionic channel, and the initial rate of binding was potentiated by receptor agonists. Equilibrium binding of [3H]PCP to Torpedo membranes was with two affinities, but in the presence of AcCho, [3H]PCP binding was with a single affinity. The affinities of channel drugs obtained by inhibition of binding of [3H]PCP and [3H[perhydrohistrionicotoxin to Torpedo membranes were different, with correlation coefficients of 0.52 and 0.82 in the absence and presence of a receptor agonist, respectively; this suggests differences in their binding sites on the ionic channel of the AcCho receptor.

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Selected References

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

  1. Adler M., Oliveira A. C., Albuquerque E. X., Mansour N. A., Eldefrawi A. T. Reaction of tetraethylammonium with the open and closed conformations of the acetylcholine receptor ionic channel complex. J Gen Physiol. 1979 Jul;74(1):129–152. doi: 10.1085/jgp.74.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albuquerque E. X., Eldefrawi A. T., Eldefrawi M. E., Mansour N. A., Tsai M. C. Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor. Science. 1978 Feb 17;199(4330):788–790. doi: 10.1126/science.622570. [DOI] [PubMed] [Google Scholar]
  3. Albuquerque E. X., Tsai M. C., Aronstam R. S., Eldefrawi A. T., Eldefrawi M. E. Sites of action of phencyclidine. II. Interaction with the ionic channel of the nicotinic receptor. Mol Pharmacol. 1980 Sep;18(2):167–178. [PubMed] [Google Scholar]
  4. Albuquerque E. X., Tsai M. C., Aronstam R. S., Witkop B., Eldefrawi A. T., Eldefrawi M. E. Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1224–1228. doi: 10.1073/pnas.77.2.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Aronstam R. S., Eldefrawi A. T., Eldefrawi M. E. Similarities in the binding sites of the muscarinic receptor and the ionic channel of the nicotinic receptor. Biochem Pharmacol. 1980 May 1;29(9):1311–1314. doi: 10.1016/0006-2952(80)90292-0. [DOI] [PubMed] [Google Scholar]
  6. CHEN G. M., WESTON J. K. The analgesic and anesthetic effect of 1-(1-phenylcyclohexyl) piperidine HCl on the monkey. Anesth Analg. 1960 Mar-Apr;39:132–137. [PubMed] [Google Scholar]
  7. Eldefrawi A. T., Eldefrawi M. E., Albuquerque E. X., Oliveira A. C., Mansour N., Adler M., Daly J. W., Brown G. B., Burgermeister W., Witkop B. Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc Natl Acad Sci U S A. 1977 May;74(5):2172–2176. doi: 10.1073/pnas.74.5.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eldefrawi M. E., Aronstam R. S., Bakry N. M., Eldefrawi A. T., Albuquerque E. X. Activation, inactivation, and desensitization of acetylcholine receptor channel complex detected by binding of perhydrohistrionicotoxin. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2309–2313. doi: 10.1073/pnas.77.4.2309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eldefrawi M. E., Eldefrawi A. T., Mansour N. A., Daly J. W., Witkop B., Albuquerque E. X. Acetylcholine receptor and ionic channel of Torpedo electroplax: binding of perhydrohistrionicotoxin to membrane and solubilized preparations. Biochemistry. 1978 Dec 12;17(25):5474–5484. doi: 10.1021/bi00618a023. [DOI] [PubMed] [Google Scholar]
  10. Elliott J., Raftery M. A. Binding of perhydrohistrionicotoxin to intact and detergent-solubilized membranes enriched in nicotinic acetylcholine receptor. Biochemistry. 1979 May 15;18(10):1868–1874. doi: 10.1021/bi00577a004. [DOI] [PubMed] [Google Scholar]
  11. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kloog Y., Kalir A., Buchman O., Sokolovsky M. Specific binding of [3H]phencyclidines to membrane preparation. Possible interaction with the cholinergic ionophore. FEBS Lett. 1980 Jan 1;109(1):125–128. doi: 10.1016/0014-5793(80)81325-1. [DOI] [PubMed] [Google Scholar]
  13. Lapa A. J., Albuquerque E. X., Sarvey J. M., Daly J., Witkop B. Effects of histrionicotoxin on the chemosensitive and electrical properties of skeletal muscle. Exp Neurol. 1975 Jun;47(3):558–580. doi: 10.1016/0014-4886(75)90088-6. [DOI] [PubMed] [Google Scholar]
  14. Tsai M. C., Albuquerque E. X., Aronstam R. S., Eldefrawi A. T., Eldefrawi M. E., Triggle D. J. Sites of action of phencyclidine. I. Effects on the electrical excitability and chemosensitive properties of the neuromuscular junction of skeletal muscle. Mol Pharmacol. 1980 Sep;18(2):159–166. [PubMed] [Google Scholar]
  15. Vincent J. P., Kartalovski B., Geneste P., Kamenka J. M., Lazdunski M. Interaction of phencyclidine ("angel dust") with a specific receptor in rat brain membranes. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4678–4682. doi: 10.1073/pnas.76.9.4678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Zukin S. R., Zukin R. S. Specific [3H]phencyclidine binding in rat central nervous system. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5372–5376. doi: 10.1073/pnas.76.10.5372. [DOI] [PMC free article] [PubMed] [Google Scholar]

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