Waglerin-1 inhibits GABA(A) current of neurons in the nucleus accumbens of neonatal rats.
The effect of Waglerin-1, a 22-amino acid peptide purified from the venom of Wagler's pit viper on the whole cell current response (I(GABA)) to gamma-aminobutyric acid (GABA) was examined for neurons freshly isolated from the nucleus accumbens of 3- to 7-day-old rats. Waglerin-1 depressed I(GABA) induced by subsaturating concentrations of GABA; the IC(50) for I(GABA) induced by 10 microM GABA was 2.5 microM Waglerin-1. This concentration of Waglerin-1 shifted the GABA concentration-response curve to the right in a parallel manner, increasing the GABA EC(50) from 12+/-3 to 27+/-5 microM. The depressant effect of Waglerin-1 was greater at negative holding potentials. Zn(2+) also inhibited I(GABA) with an IC(50) of 0.3 microM. Phosphorylation state appeared to modulate GABA(A) receptor sensitivity to the inhibitory effect of Waglerin-1 since dialysis of neurons with N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl (H-89), an inhibitor of protein kinase A, prevented inhibition. The data are discussed in terms of developmental influences on the subunit composition of GABA(A) receptors in neurons of the nucleus accumbens.
Ye
J H
JH
Departments of Anesthesiology, and Pharmacology and Physiology, New Jersey Medical School (UMDNJ), 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Ren
J
J
McArdle
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D003435:Crotalid Venoms / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D003435:Crotalid Venoms; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011963:Receptors, GABA-A; D013449:Sulfonamides; C077895:waglerin; D005680:gamma-Aminobutyric Acid; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003975:Diazepam