GABAB receptors are expressed in human aortic smooth muscle cells and regulate the intracellular Ca2+ concentration

Abstract

The aim of this study was to investigate the expression of GABAB receptors, a subclass of receptors to the inhibitory neurotransmitter gamma-aminobutyric acid (GABAB), in human aortic smooth muscle cells (HASMCs), and to explore if altering receptor activation modified intracellular Ca(2+) concentration ([Ca(2+)]i) of HASMCs. Real-time PCR, western blots and immunofluorescence were used to determine the expression of GABABR1 and GABABR2 in cultured HASMCs. Immunohistochemistry was used to localize the two subunits in human left anterior descending artery (LAD). The effects of the GABAB receptor agonist baclofen on [Ca(2+)]i in cultured HASMCs were demonstrated using fluo-3. Both GABABR1 and GABABR2 mRNA and protein were identified in cultured HASMCs and antibody staining was also localized to smooth muscle cells of human LAD. 100 μM baclofen caused a transient increase of [Ca(2+)]i in cultured HASMCs regardless of whether Ca(2+) was added to the medium, and the effects were inhibited by pre-treatment with CGP46381 (selective GABAB receptor antagonist), pertussis toxin (a Gi/o protein inhibitor), and U73122 (a phospholipase C blocker). GABAB receptors are expressed in HASMCs and regulate the [Ca(2+)]i via a Gi/o-coupled receptor pathway and a phospholipase C activation pathway.

Vascular amyloid accumulation alters the gabaergic synapse and induces hyperactivity in a model of cerebral amyloid angiopathy

“…This indirect mechanism is supported by a previous study demonstrating GABA alteration and GABA A R involvement in blood–brain barrier disruption in cerebral ischemia (Chi, Hunter, Liu, Chi, & Weiss, 2011). Interestingly, a novel study has demonstrated that GABA A R modulates the plasma membrane potential in arterial vascular smooth muscle cells (Wang, Cheng, & Schmid, 2015). As vascular amyloid triggers an impairment of vascular smooth muscle cells in CAA (Attems, 2005), GABA A R dysfunction in these vascular cells may contribute to the cerebrovascular pathology observed in CAA.…”

GABABEncephalitis: A Fifty-Two-Year-Old Man with Seizures, Dysautonomia, and Acute Heart Failure

“…Although the known etiologies of supraventricular tachycardia and acute heart failure are numerous and varied, the clinical circumstances in this case strongly suggest that they were a consequence of neurologic injury. Three points when taken together support this: (1) GABA B receptors are transcribed in the fetal but not adult heart and are thought to be found primarily in the nervous system, though they have recently been described in smooth muscle of the human aorta [ 6 , 7 ]; (2) the cardiomyopathy persisted until the patient underwent immunosuppressive treatment and then fully resolved with treatment; (3) there are few etiologies of his cardiomyopathy identified which would be expected to resolve with immunosuppression or spontaneously, though autoimmune myocarditis or tachycardia-induced cardiomyopathy is among them.…”

GABAA and GABAB Receptors Mediate GABA-Induced Intracellular Ca2+ Signals in Human Brain Microvascular Endothelial Cells

“…Ca 2+ imaging recordings showed that 100 µM GABA elicits a robust biphasic elevation in [Ca 2+ ] i in hCMEC/D3 cells, and this concentration was used to unveil the underlying signaling pathways. Notably, GABA-induced intracellular Ca 2+ waves have been observed in many cell types that do not belong to the NVU, including HAECs [ 64 ], human aortic smooth muscle cells [ 71 ], mouse embryonic stem cells [ 72 ], and the human breast cancer cell line, MCF7 [ 24 ].…”