Temperature-dependent effect of zolpidem on the GABAA receptor-mediated response at recombinant human GABAA receptor subtypes.
The effects of zolpidem on the two forms of recombinant human GABAA receptors (alpha1beta2gamma2s and alpha3beta2gamma2s) at different temperatures were functionally investigated, using the whole-cell patch recording configuration. In both forms, zolpidem potentiated the response to GABA in a concentration-dependent manner. At 16 degrees C, the apparent dissociation constant (KD) values for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 3.7 x 10(-8) and 5.6 x 10(-7) M, respectively. When the temperature was increased to 36 degrees C, the KD values for the alpha1beta2gamma2s and alpha3beta2gamma2s forms were 2.1 x 10(-7) and 1.5 x 10(-6) M, respectively. Although the affinity ratio was reduced from 15.1 to 7.1-fold the selectivity of zolpidem for the alpha1beta2gamma2s still remained at 36 degrees C.
Department of Pediatrics, Tohoku University School of Medicine, Sendai 980-77, Japan.
M
M
Munakata
Y H
YH
Jin
N
N
Akaike
M
M
Nielsen
D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects; D013696:Temperature; D000077334:Zolpidem
D018755:GABA Agonists; D011725:Pyridines; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D000077334:Zolpidem