TY - JOUR

T1 - Profiling of GABAA and GABAB receptor expression in the myometrium of the human uterus

AU - Söderhielm, Pella Cecilia

AU - Klein, Anders Bue

AU - Bomholtz, Sofia Hammami

AU - Jensen, Anders A.

PY - 2018

Y1 - 2018

N2 - AbstractAims: gamma-aminobutyric acid (GABA) mediates its physiological effects through the GABA(A) and GABA(B) receptors. In this study the putative expression of GABA(A)R and GABA(B)R subunits in human myometrium tissue was investigated. Main methods: The expression levels of the 19 GABA(A)R subunits (alpha(1)-alpha(6),beta(1)-beta(3), gamma(1)-gamma(3), delta, epsilon, pi, theta, rho(1)-rho(3)) and the three GABA(B)R subunits (GABA(B1a), GABA(B1b), GABA(B2)) were characterized by RT-qPCR analysis on two commercial samples and six samples derived from surgically removed myometrial tissues from different women. We probed for functional GABA(A)R expression in primary human myometrial smooth muscle cells (HMSMCs) by whole-cell patch-clamp electrophysiology. Key findings: The absolute mRNA levels of the 22 GABA(A)R and GABA(B)R genes varied considerably across the eight samples, but a pronounced overlap existed between the specific subunits detected in the samples, with alpha(2), beta(2) , beta(3), epsilon, pi, theta, GABA(B1a) and GABA(B1b) mRNAs being detected in most samples. The expression profile of GABA(A)R and GABA(B)R subunit mRNAs in HMSMCs correlated with that observed in the eight tissue samples, albeit the subunit transcripts were detected at lower relative levels. Neither muscimol nor GABA evoked significant currents in these cells in the patch-clamp recordings. Significance: While the expression of the GABA(B1) subunits on their own is unlikely to give rise to functional GABA(B)R expression, the GABA(A)R subunits identified at mRNA level would be able to form functional receptors in the human myometrial tissue. Although GABA(A)R-mediated currents could not be recorded from HMSMCs in this study, this suggests a role for GABAergic transmission in the human myometrium

AB - AbstractAims: gamma-aminobutyric acid (GABA) mediates its physiological effects through the GABA(A) and GABA(B) receptors. In this study the putative expression of GABA(A)R and GABA(B)R subunits in human myometrium tissue was investigated. Main methods: The expression levels of the 19 GABA(A)R subunits (alpha(1)-alpha(6),beta(1)-beta(3), gamma(1)-gamma(3), delta, epsilon, pi, theta, rho(1)-rho(3)) and the three GABA(B)R subunits (GABA(B1a), GABA(B1b), GABA(B2)) were characterized by RT-qPCR analysis on two commercial samples and six samples derived from surgically removed myometrial tissues from different women. We probed for functional GABA(A)R expression in primary human myometrial smooth muscle cells (HMSMCs) by whole-cell patch-clamp electrophysiology. Key findings: The absolute mRNA levels of the 22 GABA(A)R and GABA(B)R genes varied considerably across the eight samples, but a pronounced overlap existed between the specific subunits detected in the samples, with alpha(2), beta(2) , beta(3), epsilon, pi, theta, GABA(B1a) and GABA(B1b) mRNAs being detected in most samples. The expression profile of GABA(A)R and GABA(B)R subunit mRNAs in HMSMCs correlated with that observed in the eight tissue samples, albeit the subunit transcripts were detected at lower relative levels. Neither muscimol nor GABA evoked significant currents in these cells in the patch-clamp recordings. Significance: While the expression of the GABA(B1) subunits on their own is unlikely to give rise to functional GABA(B)R expression, the GABA(A)R subunits identified at mRNA level would be able to form functional receptors in the human myometrial tissue. Although GABA(A)R-mediated currents could not be recorded from HMSMCs in this study, this suggests a role for GABAergic transmission in the human myometrium

U2 - 10.1016/j.lfs.2018.10.033

DO - 10.1016/j.lfs.2018.10.033

M3 - Journal article

C2 - 30343129

VL - 214

SP - 145

EP - 152

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -