TY  - JOUR
AU  - Gajić-Bojić, Milica
AU  - Todorović, Lidija
AU  - Santrač, Anja
AU  - Mian, Md Yeunus
AU  - Sharmin, Dishary
AU  - Cook, James M.
AU  - Savić, Miroslav M.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9163
AB  - Different subtypes of GABAA (gamma-aminobutyric acid A) receptors, through their specific regional and cellular localization, are involved in the manifestation of various functions, both at the central and peripheral levels. We hypothesized that various non-neuronal GABAA receptors are expressed on blood vessels, through which positive allosteric modulators of GABAA receptors exhibit vasodilatory effects. This study involved two parts: one to determine the presence of α1-6 subunit GABAA receptor mRNAs in the rat thoracic aorta, and the other to determine the vasoactivity of the various selective and non-selective positive GABAA receptor modulators: zolpidem (α1-selective), XHe–III–074 (α4-selective), MP–III–022 (α5-selective), DK-I-56-1 (α6-selective), SH-I-048A and diazepam (non-selective). Reverse transcription-polymerase chain reaction (RT-PCR) analysis data demonstrated for the first time the expression of α1, α2, α3, α4 and α5 subunits in the rat thoracic aorta tissue. Tissue bath assays on isolated rat aortic rings revealed significant vasodilatory effects of diazepam, SH-I-048A, XHe–III–074, MP–III–022 and DK-I-56-1, all in terms of achieved relaxations (over 50% of relative tension decrease), as well as in terms of preventive effects on phenylephrine (PE) contraction. Diazepam was the most efficient ligand in the present study, while zolpidem showed the weakest vascular effects. In addition, diazepam-induced relaxations in the presence of antagonists PK11195 or bicuculline were significantly reduced (P < 0.001 and P < 0.05, respectively) at lower concentrations of diazepam (10−7 M and 3 × 10−7 M). The present work suggests that the observed vasoactivity is due to modulation of “vascular” GABAA receptors, which after further detailed research may provide a therapeutic target. © 2021 Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta
VL  - 899
SP  - 174023
DO  - 10.1016/j.ejphar.2021.174023
ER  - 

@article{
author = "Gajić-Bojić, Milica and Todorović, Lidija and Santrač, Anja and Mian, Md Yeunus and Sharmin, Dishary and Cook, James M. and Savić, Miroslav M.",
year = "2021",
abstract = "Different subtypes of GABAA (gamma-aminobutyric acid A) receptors, through their specific regional and cellular localization, are involved in the manifestation of various functions, both at the central and peripheral levels. We hypothesized that various non-neuronal GABAA receptors are expressed on blood vessels, through which positive allosteric modulators of GABAA receptors exhibit vasodilatory effects. This study involved two parts: one to determine the presence of α1-6 subunit GABAA receptor mRNAs in the rat thoracic aorta, and the other to determine the vasoactivity of the various selective and non-selective positive GABAA receptor modulators: zolpidem (α1-selective), XHe–III–074 (α4-selective), MP–III–022 (α5-selective), DK-I-56-1 (α6-selective), SH-I-048A and diazepam (non-selective). Reverse transcription-polymerase chain reaction (RT-PCR) analysis data demonstrated for the first time the expression of α1, α2, α3, α4 and α5 subunits in the rat thoracic aorta tissue. Tissue bath assays on isolated rat aortic rings revealed significant vasodilatory effects of diazepam, SH-I-048A, XHe–III–074, MP–III–022 and DK-I-56-1, all in terms of achieved relaxations (over 50% of relative tension decrease), as well as in terms of preventive effects on phenylephrine (PE) contraction. Diazepam was the most efficient ligand in the present study, while zolpidem showed the weakest vascular effects. In addition, diazepam-induced relaxations in the presence of antagonists PK11195 or bicuculline were significantly reduced (P < 0.001 and P < 0.05, respectively) at lower concentrations of diazepam (10−7 M and 3 × 10−7 M). The present work suggests that the observed vasoactivity is due to modulation of “vascular” GABAA receptors, which after further detailed research may provide a therapeutic target. © 2021 Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta",
volume = "899",
pages = "174023",
doi = "10.1016/j.ejphar.2021.174023"
}

Gajić-Bojić, M., Todorović, L., Santrač, A., Mian, M. Y., Sharmin, D., Cook, J. M.,& Savić, M. M.. (2021). Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta. in European Journal of Pharmacology, 899, 174023.
https://doi.org/10.1016/j.ejphar.2021.174023

Gajić-Bojić M, Todorović L, Santrač A, Mian MY, Sharmin D, Cook JM, Savić MM. Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta. in European Journal of Pharmacology. 2021;899:174023.
doi:10.1016/j.ejphar.2021.174023 .

Gajić-Bojić, Milica, Todorović, Lidija, Santrač, Anja, Mian, Md Yeunus, Sharmin, Dishary, Cook, James M., Savić, Miroslav M., "Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta" in European Journal of Pharmacology, 899 (2021):174023,
https://doi.org/10.1016/j.ejphar.2021.174023 . .