Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.

Publication ,  Journal Article
Morrisett, RA; Chow, CC; Sakaguchi, T; Shin, C; McNamara, JO
Published in: J Neurochem
May 1990

The intent of this work was to elucidate the mechanism by which N-methyl-D-aspartate (NMDA) receptor agonists inhibit a second messenger system, namely, the stimulation of phosphoinositide (PI) hydrolysis activated by muscarinic cholinergic receptor agonists. NMDA inhibited cholinergic stimulation of PI hydrolysis in a dose- and time-dependent manner. NMDA exerts this effect indirectly through channel activation, because both MK-801 and N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) prevented this action. Prevention of the NMDA effect by removal of sodium, but not calcium, from the incubation buffer suggested that depolarization may be the responsible mechanism. Depolarization alone proved sufficient to inhibit cholinergic activation of PI hydrolysis, because both veratridine and an elevated extracellular potassium level inhibited cholinergic stimulation of PI hydrolysis. The effect of NMDA appeared to require sodium flux through NMDA channels rather than through voltage-dependent sodium channels, because tetrodotoxin failed to inhibit the effect of NMDA. In correlative electrophysiologic experiments, NMDA profoundly inhibited evoked excitatory postsynaptic potentials and population action potentials of CA1 neurons, an effect almost certainly due to depolarization. The dose and time course of the electrophysiologic effects correlated well with the biochemical effects. Taken together, the data support the assertion that NMDA receptor activation inhibits PI hydrolysis by depolarization mediated by sodium flux through NMDA channels.

Duke Scholars

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

May 1990

Volume

54

Issue

5

Start / End Page

1517 / 1525

Location

England

Related Subject Headings

  • Veratridine
  • Second Messenger Systems
  • Rats, Inbred Strains
  • Rats
  • Protein Kinase C
  • Potassium
  • Phosphatidylinositols
  • Neurology & Neurosurgery
  • N-Methylaspartate
  • Muscarine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morrisett, R. A., Chow, C. C., Sakaguchi, T., Shin, C., & McNamara, J. O. (1990). Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation. J Neurochem, 54(5), 1517–1525. https://doi.org/10.1111/j.1471-4159.1990.tb01199.x
Morrisett, R. A., C. C. Chow, T. Sakaguchi, C. Shin, and J. O. McNamara. “Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.J Neurochem 54, no. 5 (May 1990): 1517–25. https://doi.org/10.1111/j.1471-4159.1990.tb01199.x.
Morrisett RA, Chow CC, Sakaguchi T, Shin C, McNamara JO. Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation. J Neurochem. 1990 May;54(5):1517–25.
Morrisett, R. A., et al. “Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.J Neurochem, vol. 54, no. 5, May 1990, pp. 1517–25. Pubmed, doi:10.1111/j.1471-4159.1990.tb01199.x.
Morrisett RA, Chow CC, Sakaguchi T, Shin C, McNamara JO. Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation. J Neurochem. 1990 May;54(5):1517–1525.
Journal cover image

Published In

J Neurochem

DOI

ISSN

0022-3042

Publication Date

May 1990

Volume

54

Issue

5

Start / End Page

1517 / 1525

Location

England

Related Subject Headings

  • Veratridine
  • Second Messenger Systems
  • Rats, Inbred Strains
  • Rats
  • Protein Kinase C
  • Potassium
  • Phosphatidylinositols
  • Neurology & Neurosurgery
  • N-Methylaspartate
  • Muscarine