Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices

Marvin E. Myles, Yesim Polar, John N. Fain

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The present studies examined the inhibitory effect of veratridine (a Na+ channel activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. Veratridine inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation (after a delay of about 30 seconds) at 60 or 120 seconds when there was little inhibition of inositol 1,4,5 trisphophate accumulation. The inhibitory effect of veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate accumulation was abolished in the presence of ouabain or tetrodotoxin but was unaffected in low calcium conditions. Veratridine reduced the total ATP content and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but not 30 μM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in the presence of carbachol was reversed by the presence of exogenous 8-bromo cyclic AMP or forskolin which activates adenylylcyclase. However, the decrease in brain slice ATP seen in the presence of veratridine was unaffected by forskolin. Our results are compatible with the hypothesis that veratridine inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5-P3.

Original languageEnglish (US)
Pages (from-to)1057-1064
Number of pages8
JournalNeurochemical Research
Volume20
Issue number9
DOIs
StatePublished - Sep 1995
Externally publishedYes

Fingerprint

Veratridine
Carbachol
Inositol
Rats
Brain
Adenosine Triphosphate
Tetrodotoxin
Colforsin
8-Bromo Cyclic Adenosine Monophosphate
Cholinergic Agonists
Ouabain
inositol-1,3,4,5-tetrakisphosphate
Calcium

Keywords

  • brain cortical slices
  • inositol 1,3,4,5-tetrakisphosphate
  • muscarinic receptors
  • Phosphoinositide breakdown
  • veratridine

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices. / Myles, Marvin E.; Polar, Yesim; Fain, John N.

In: Neurochemical Research, Vol. 20, No. 9, 09.1995, p. 1057-1064.

Research output: Contribution to journalArticle

@article{6229c3c23822442a86cfa0694dcf163d,
title = "Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices",
abstract = "The present studies examined the inhibitory effect of veratridine (a Na+ channel activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. Veratridine inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation (after a delay of about 30 seconds) at 60 or 120 seconds when there was little inhibition of inositol 1,4,5 trisphophate accumulation. The inhibitory effect of veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate accumulation was abolished in the presence of ouabain or tetrodotoxin but was unaffected in low calcium conditions. Veratridine reduced the total ATP content and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but not 30 μM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in the presence of carbachol was reversed by the presence of exogenous 8-bromo cyclic AMP or forskolin which activates adenylylcyclase. However, the decrease in brain slice ATP seen in the presence of veratridine was unaffected by forskolin. Our results are compatible with the hypothesis that veratridine inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5-P3.",
keywords = "brain cortical slices, inositol 1,3,4,5-tetrakisphosphate, muscarinic receptors, Phosphoinositide breakdown, veratridine",
author = "Myles, {Marvin E.} and Yesim Polar and Fain, {John N.}",
year = "1995",
month = "9",
doi = "10.1007/BF00995560",
language = "English (US)",
volume = "20",
pages = "1057--1064",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "9",

}

TY - JOUR

T1 - Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices

AU - Myles, Marvin E.

AU - Polar, Yesim

AU - Fain, John N.

PY - 1995/9

Y1 - 1995/9

N2 - The present studies examined the inhibitory effect of veratridine (a Na+ channel activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. Veratridine inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation (after a delay of about 30 seconds) at 60 or 120 seconds when there was little inhibition of inositol 1,4,5 trisphophate accumulation. The inhibitory effect of veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate accumulation was abolished in the presence of ouabain or tetrodotoxin but was unaffected in low calcium conditions. Veratridine reduced the total ATP content and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but not 30 μM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in the presence of carbachol was reversed by the presence of exogenous 8-bromo cyclic AMP or forskolin which activates adenylylcyclase. However, the decrease in brain slice ATP seen in the presence of veratridine was unaffected by forskolin. Our results are compatible with the hypothesis that veratridine inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5-P3.

AB - The present studies examined the inhibitory effect of veratridine (a Na+ channel activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. Veratridine inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation (after a delay of about 30 seconds) at 60 or 120 seconds when there was little inhibition of inositol 1,4,5 trisphophate accumulation. The inhibitory effect of veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate accumulation was abolished in the presence of ouabain or tetrodotoxin but was unaffected in low calcium conditions. Veratridine reduced the total ATP content and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but not 30 μM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in the presence of carbachol was reversed by the presence of exogenous 8-bromo cyclic AMP or forskolin which activates adenylylcyclase. However, the decrease in brain slice ATP seen in the presence of veratridine was unaffected by forskolin. Our results are compatible with the hypothesis that veratridine inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5-P3.

KW - brain cortical slices

KW - inositol 1,3,4,5-tetrakisphosphate

KW - muscarinic receptors

KW - Phosphoinositide breakdown

KW - veratridine

UR - http://www.scopus.com/inward/record.url?scp=0028809845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028809845&partnerID=8YFLogxK

U2 - 10.1007/BF00995560

DO - 10.1007/BF00995560

M3 - Article

C2 - 8570010

AN - SCOPUS:0028809845

VL - 20

SP - 1057

EP - 1064

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 9

ER -