title: Regulation of α3-containing GABAA receptors in guinea-pig adrenal medullary cells by adrenal steroids.
abstract: GABA is thought to function as a paracrine factor in adrenal medullary (AM) cells. Thus, we electrophysiologically and immunologically examined the properties of GABAA receptors (GABAARs) in guinea-pig AM cells. Bath application of GABA produced an inward current at -60 mV in a dose-dependent manner with an EC50 of 32.3 μM. This GABA-induced current was enhanced by allopregnanolone at concentrations of 0.01 μM and more. A prior exposure to allopregnanolone resulted in a decrease in an EC50 for GABA in activating GABAARs. The GABA-induced current was suppressed by Zn(2+) in a dose-dependent manner with an IC50 of 18 μM, whereas it was enhanced by 100 μM La(3+). The benzodiazepine analog diazepam was three times more potent than zolpidem in enhancing the GABA current, and it was also augmented by L-838,417, which has no action on α1-containing GABAARs. The GABAAR α3, but not α1, and γ2 subunits were immunologically detected at the cell periphery. The expression of α3 subunits in PC12 cells was enhanced by glucocorticoid activity. The results indicated that GABAARs in guinea-pig AM cells mainly comprise α3, β, and γ2 subunits and are enhanced by allopreganalone and glucocorticoids may play a major role in the expression of α3 subunits.
authors.affiliation: Department of Cell and Systems Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu 807-8555, Japan. Electronic address: minoue@med.uoeh-u.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism*; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D011280:Pregnanolone / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000021:Abortifacient Agents, Steroidal; D000777:Anesthetics; D002352:Carrier Proteins; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D013256:Steroids; C073441:gephyrin; D015735:Mifepristone; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone; D015032:Zinc
keywords: AM; Ab; DHEAS; DMSO; GABA; GABA(A) receptor; GABA(A)R; Hepes; IRs; PAGE; PBS-T; PC12; PVDF; RT-PCR; SDS; adrenal medullary; antibody; chromaffin cell; dehydroepiandrostedione sulfate; dimethyl sulfoxide; glucocorticoid; hydroxyethyl piperazineethanesulfonic acid; immunoreactivities; phosphate-buffered saline with Tween 20; polyacrylamide gel electrophoresis; polyvinylidene difluoride; receptor; reverse transcriptase-polymerase chain reaction; sodium dodecyl sulfate; steroid hormone