Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta

Different subtypes of GABAA (gamma-aminobutyric acid A) receptors, through their specific regional and cellular localization, are involved in the manifestation various functions, both at central peripheral levels. We hypothesized that non-neuronal receptors expressed on blood vessels, which positive allosteric modulators exhibit vasodilatory effects. This study two parts: one to determine presence ?1-6 subunit receptor mRNAs rat thoracic aorta, other vasoactivity selective non-selective modulators: zolpidem (?1-selective), XHe–III–074 (?4-selective), MP–III–022 (?5-selective), DK-I-56-1 (?6-selective), SH-I-048A diazepam (non-selective). Reverse transcription-polymerase chain reaction (RT-PCR) analysis data demonstrated for first time expression ?1, ?2, ?3, ?4 ?5 subunits aorta tissue. Tissue bath assays isolated aortic rings revealed significant effects diazepam, SH-I-048A, XHe–III–074, DK-I-56-1, all terms achieved relaxations (over 50% relative tension decrease), as well preventive phenylephrine (PE) contraction. Diazepam was most efficient ligand present study, while showed weakest vascular In addition, diazepam-induced antagonists PK11195 or bicuculline were significantly reduced (P < 0.001 P 0.05, respectively) lower concentrations (10?7 M 3 × 10?7 M). The work suggests observed is due modulation “vascular” after further detailed research may provide a therapeutic target.