A novel functional role for the classic CNS neurotransmitters, GABA, glycine, and glutamate, in the kidney: potent and opposing regulators of the renal vasculature
Wildman, Scott, Dunn, Kadeshia, Van Beusecum, Justin P, Inscho, Edward W, Kelley, Stephen, Lilley, Rebecca J, Cook, Anthony K, Taylor, Kirsti D. and Peppiatt-Wildman, Claire M. (2023) A novel functional role for the classic CNS neurotransmitters, GABA, glycine, and glutamate, in the kidney: potent and opposing regulators of the renal vasculature. American Journal of Physiology-Renal Physiology, 324. ISSN 1931-857X
Abstract
The presence of a renal GABA/glutamate system has previously been described; however, its functional significance in the kidney remains undefined. We hypothesized, given its extensive presence in the kidney, that activation of this GABA/glutamate system would elicit a vasoactive response from the renal microvessels. The functional data here demonstrate, for the first time, that activation of endogenous GABA and glutamate receptors in the kidney significantly alters microvessel diameter with important implications for influencing renal blood flow. Renal blood flow is regulated in both the renal cortical and medullary microcirculatory beds via diverse signaling pathways. GABA- and glutamate-mediated effects on renal capillaries are strikingly similar to those central to the regulation of central nervous system capillaries, that is, exposing renal tissue to physiological concentrations of GABA, glutamate, and glycine led to alterations in the way that contractile cells, pericytes, and smooth muscle cells, regulate microvessel diameter in the kidney. Since dysregulated renal blood flow is linked to chronic renal disease, alterations in the renal GABA/glutamate system, possibly through prescription drugs, could significantly impact long-term kidney function.NEW & NOTEWORTHY Functional data here offer novel insight into the vasoactive activity of the renal GABA/glutamate system. These data show that activation of endogenous GABA and glutamate receptors in the kidney significantly alters microvessel diameter. Furthermore, the results show that these antiepileptic drugs are as potentially challenging to the kidney as nonsteroidal anti-inflammatory drugs.
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