Effects of phencyclidine and its derivatives on enteric neurones

A. R. Gintzler, R. Suzanne Zukin, S. R. Zukin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The effects of N-(1-phenylcyclohexyl)piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.

Original languageEnglish (US)
Pages (from-to)261-267
Number of pages7
JournalBritish Journal of Pharmacology
Volume75
Issue number2
StatePublished - 1982

Fingerprint

Phencyclidine
Neurons
Guinea Pigs
Ileum
tenocyclidine
Naloxone
Binding Sites
Myenteric Plexus
Narcotic Antagonists
Ketamine
Cholinergic Receptors
piperidine
Atropine
Morphine
Cholinergic Agents
Acetylcholine
Central Nervous System
Muscles
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of phencyclidine and its derivatives on enteric neurones. / Gintzler, A. R.; Zukin, R. Suzanne; Zukin, S. R.

In: British Journal of Pharmacology, Vol. 75, No. 2, 1982, p. 261-267.

Research output: Contribution to journalArticle

@article{fd201e0ec1e4409681cd47904962899f,
title = "Effects of phencyclidine and its derivatives on enteric neurones",
abstract = "The effects of N-(1-phenylcyclohexyl)piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.",
author = "Gintzler, {A. R.} and Zukin, {R. Suzanne} and Zukin, {S. R.}",
year = "1982",
language = "English (US)",
volume = "75",
pages = "261--267",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Effects of phencyclidine and its derivatives on enteric neurones

AU - Gintzler, A. R.

AU - Zukin, R. Suzanne

AU - Zukin, S. R.

PY - 1982

Y1 - 1982

N2 - The effects of N-(1-phenylcyclohexyl)piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.

AB - The effects of N-(1-phenylcyclohexyl)piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.

UR - http://www.scopus.com/inward/record.url?scp=0020076118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020076118&partnerID=8YFLogxK

M3 - Article

C2 - 6313107

AN - SCOPUS:0020076118

VL - 75

SP - 261

EP - 267

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -