Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115)

Michael Mckinney, Michael Pfenning, Elliott Richelson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 μM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an ic50 of 450 μm. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki, value of 162 μM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki, for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 μM. Caracemide was a competitive inhibitor of acetylcholinesterase with a K1, value of 8 μM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.

Original languageEnglish (US)
Pages (from-to)2615-2622
Number of pages8
JournalBiochemical Pharmacology
Volume35
Issue number15
DOIs
StatePublished - Aug 1 1986

Fingerprint

Clone cells
Neurochemistry
Neuroblastoma
Antineoplastic Agents
Clone Cells
Alprostadil
Muscarinic Receptors
Adenylyl Cyclases
Guanylate Cyclase
Cyclic GMP
Pharmaceutical Preparations
Histamine Receptors
Cholinesterase Inhibitors
Monoamine Oxidase
Neurology
Nitroprusside
Colforsin
caracemide
Cyclic AMP
Nervous System

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115). / Mckinney, Michael; Pfenning, Michael; Richelson, Elliott.

In: Biochemical Pharmacology, Vol. 35, No. 15, 01.08.1986, p. 2615-2622.

Research output: Contribution to journalArticle

Mckinney, Michael ; Pfenning, Michael ; Richelson, Elliott. / Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115). In: Biochemical Pharmacology. 1986 ; Vol. 35, No. 15. pp. 2615-2622.
@article{57ab9bcd6b4748668c047499f8078100,
title = "Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115)",
abstract = "Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 μM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an ic50 of 450 μm. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki, value of 162 μM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki, for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 μM. Caracemide was a competitive inhibitor of acetylcholinesterase with a K1, value of 8 μM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.",
author = "Michael Mckinney and Michael Pfenning and Elliott Richelson",
year = "1986",
month = "8",
day = "1",
doi = "10.1016/0006-2952(86)90061-4",
language = "English (US)",
volume = "35",
pages = "2615--2622",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "15",

}

TY - JOUR

T1 - Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115)

AU - Mckinney, Michael

AU - Pfenning, Michael

AU - Richelson, Elliott

PY - 1986/8/1

Y1 - 1986/8/1

N2 - Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 μM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an ic50 of 450 μm. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki, value of 162 μM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki, for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 μM. Caracemide was a competitive inhibitor of acetylcholinesterase with a K1, value of 8 μM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.

AB - Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 μM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an ic50 of 450 μm. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki, value of 162 μM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki, for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 μM. Caracemide was a competitive inhibitor of acetylcholinesterase with a K1, value of 8 μM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.

UR - http://www.scopus.com/inward/record.url?scp=0022496374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022496374&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(86)90061-4

DO - 10.1016/0006-2952(86)90061-4

M3 - Article

C2 - 2874811

AN - SCOPUS:0022496374

VL - 35

SP - 2615

EP - 2622

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 15

ER -