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A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine.

Publication ,  Journal Article
Janumpalli, S; Butler, LS; MacMillan, LB; Limbird, LE; McNamara, JO
Published in: J Neurosci
March 15, 1998

Norepinephrine serves as a neurotransmitter for a population of neurons the cell bodies of which reside in a brainstem nucleus and the axons of which project widely to discrete subsets of forebrain neurons. Norepinephrine powerfully inhibits epileptogenesis in the kindling model. Pharmacological methods have demonstrated that the antiepileptogenic actions of norepinephrine are exerted via alpha2 adrenergic receptors residing on targets of noradrenergic neurons. The existence of three alpha2 adrenergic receptor subtypes together with the lack of subtype-specific ligands has precluded understanding the role of individual alpha2 adrenergic receptor subtypes in the antiepileptogenic actions of norepinephrine. Gene targeting was used to introduce a point mutation into the alpha2A adrenergic subtype in the mouse genome. The mutation produced a marked enhancement of epileptogenesis and abolished the proepileptogenic actions of the alpha2 adrenergic receptor antagonist idazoxan. These studies reveal the crucial contribution of the alpha2A receptor subtype in suppression of epileptogenesis. Development of agents that promote selective activation of the alpha2A receptor subtype may provide novel therapeutic strategies for the prophylaxis of epilepsy.

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Published In

J Neurosci

DOI

ISSN

0270-6474

Publication Date

March 15, 1998

Volume

18

Issue

6

Start / End Page

2004 / 2008

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, alpha
  • Point Mutation
  • Norepinephrine
  • Neurology & Neurosurgery
  • Mice, Mutant Strains
  • Mice
  • Kindling, Neurologic
  • Idazoxan
  • Epilepsy
  • Electrophysiology
 

Citation

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Janumpalli, S., Butler, L. S., MacMillan, L. B., Limbird, L. E., & McNamara, J. O. (1998). A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. J Neurosci, 18(6), 2004–2008. https://doi.org/10.1523/JNEUROSCI.18-06-02004.1998
Janumpalli, S., L. S. Butler, L. B. MacMillan, L. E. Limbird, and J. O. McNamara. “A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine.J Neurosci 18, no. 6 (March 15, 1998): 2004–8. https://doi.org/10.1523/JNEUROSCI.18-06-02004.1998.
Janumpalli S, Butler LS, MacMillan LB, Limbird LE, McNamara JO. A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. J Neurosci. 1998 Mar 15;18(6):2004–8.
Janumpalli, S., et al. “A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine.J Neurosci, vol. 18, no. 6, Mar. 1998, pp. 2004–08. Pubmed, doi:10.1523/JNEUROSCI.18-06-02004.1998.
Janumpalli S, Butler LS, MacMillan LB, Limbird LE, McNamara JO. A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. J Neurosci. 1998 Mar 15;18(6):2004–2008.

Published In

J Neurosci

DOI

ISSN

0270-6474

Publication Date

March 15, 1998

Volume

18

Issue

6

Start / End Page

2004 / 2008

Location

United States

Related Subject Headings

  • Receptors, Adrenergic, alpha
  • Point Mutation
  • Norepinephrine
  • Neurology & Neurosurgery
  • Mice, Mutant Strains
  • Mice
  • Kindling, Neurologic
  • Idazoxan
  • Epilepsy
  • Electrophysiology