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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Waglerin-1 Modulates γ-Aminobutyric Acid Activated Current of Murine Hypothalamic Neurons

Jiang-Hong Ye and Joseph J. McArdle
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 74-80;
Jiang-Hong Ye
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Joseph J. McArdle
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Abstract

We examined the effect of Waglerin-1, a peptide of 22 amino acid residues purified from the venom of Wagler’s pit viper (Trimeresurus wagleri), on the whole cell current response (IGABA) of freshly isolated murine hypothalamic neurons to γ-aminobutyric acid (GABA). Although the application of 32 μM Waglerin-1 alone had no effect on membrane conductance, coapplication with GABA increased IGABA for 78 and suppressed IGABA for 44 of the 141 neurons examined. The potentiating effect of Waglerin-1 was associated with a leftward shift of the concentration-response relation of GABA without increasing peak IGABA. This potentiating effect of Waglerin-1 on IGABA mimics diazepam. Furthermore, the benzodiazepine antagonist flumazenil antagonized Waglerin-1 potentiation of IGABA. These observations suggest that Waglerin-1 acts on the benzodiazepine site of one type of GABAAreceptor/channel complex to increase its affinity for agonist. In contrast, the depressant effect of Waglerin-1 was associated with a rightward shift of the concentration-response relation of GABA without depressing the maximal IGABA; this suggests a competitive inhibition of a second class of GABAR. The ability of Waglerin-1 to suppress IGABA showed a positive correlation with a similar action of Zn++. As with Zn++, the depressant effect of Waglerin-1 on IGABA was more pronounced at negative holding potentials. These observations are discussed in terms of variation in the subunit composition of GABA receptors that murine central nervous system neurons express.

Footnotes

  • Send reprint requests to: Dr. Joseph J. McArdle, Department of Pharmacology & Physiology, New Jersey Medical School (UMDNJ), 185 South Orange Ave., Newark, NJ 07103-2714.

  • ↵1 This work was supported by National Institutes of Health Grant NS31040.

  • Abbreviations:
    GABA
    γ-aminobutyric acid
    IGABA
    chloride current in response to GABA
    GABARs
    GABA receptors
    VMH
    ventromedial hypothalamus
    • Received August 26, 1996.
    • Accepted March 7, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
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Waglerin-1 Modulates γ-Aminobutyric Acid Activated Current of Murine Hypothalamic Neurons

Jiang-Hong Ye and Joseph J. McArdle
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 74-80;

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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Waglerin-1 Modulates γ-Aminobutyric Acid Activated Current of Murine Hypothalamic Neurons

Jiang-Hong Ye and Joseph J. McArdle
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 74-80;
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