The γ-aminobutyric Acid (GABA) Receptor-mediated Signal Pathway And Its Regulation On The Diameter Of Cerebral Blood Vessels

The function of astrocytes in the brain is by no means limited to just providing structural and metabolic support to neurons. In the central nervous system, the relationship between astrocytes and cerebral blood vessels is compacted and interactive. It is known to all that the elevation of the intracellular calcium concentration in astrocytes can dilate or contract the end feet-butted cerebral blood vessels. GABA is a neural transmitter, which can evoke glial calcium transients through activation of either GABA_A or GABA_B receptors in astrocytes. GABA receptors have been found on the endothelial surface of cerebral blood vessels. Based on the above findings, we speculated that GABA mediates the vasomotor response of the cerebral blood vessel indirectly through calcium transients along syncytial glial pathway and directly through the extracellular pathway to act on the blood-vessel-associated GABA receptors. To study the GABA-mediated blood vessel dilation and contraction, we applied a variety of different approaches to delineate the glial and extracellular signal pathways. To study the role of glial calcium transients, GABA-mediated vasoresponses were observed in the presence of Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM), or with a bathing medium containing zero calcium. Experiments indicate that chelating calcium concentration in the astrocytes effectively blocked GABA-induced vasodilation. Application of TTX did not alter GABA-induced vasodilation or construction, indicating that neuronal activity was not necessarily involved in the GABA-mediated vasoresponse. Application of GABA_A receptor antagonists reversed the GABA-mediated vasoresponse from dilation to constriction, implying that GABA_A receptors located on either astrocytes or blood vessels are involved in the dialation process. Application of indomethacin, an antagonist for the synthetase of prostaglandin E2 PGE2, prevented the GABA_B-mediated vasoconstriction, implying that PGE2 is involved in the GABA-mediated constriction.