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A novel functional role for classic CNS neurotransmitters, GABA, glycine and glutamate, in the kidney: potent and opposing regulators of the renal vasculature

Wildman, Scott S.P., Dunn, Kadeshia, Van Beusecum, Justin P., Inscho, Edward W., Kelley, Stephen P., Lilley, Rebecca, Cook, Anthony K., Taylor, Kirsti D., Peppiatt-Wildman, Claire M. (2023) A novel functional role for classic CNS neurotransmitters, GABA, glycine and glutamate, in the kidney: potent and opposing regulators of the renal vasculature. American Journal of Physiology-Renal Physiology, 325 (1). F38-F49. ISSN 1931-857X. E-ISSN 1522-1466. (doi:10.1152/ajprenal.00425.2021) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:101141)

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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. 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 CNS capillaries, that is, exposing renal tissue to physiological concentrations of GABA, glutamate and glycine led to alterations in the way contractile cells, perictyes 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. Key words: GABA, glutamate, Glycine, microvascular function, pericytes.

New and Noteworthy: Functional data here offers novel insight into the vasoactive activity of the renal GABA/glutamate system. This data shows that activation of endogenous GABA and glutamate receptors in the kidney significantly alters microvessel diameter. Furthermore, it shows that these antiepileptic drugs are as potentially challenging to the kidney as NSAIDs.

Item Type: Article
DOI/Identification number: 10.1152/ajprenal.00425.2021
Projects: Investigating the role of the GABA/ glutamate system in the mammalian kidney
Uncontrolled keywords: GABA; pericytes; glutamate; renal blood flow; Glycine
Subjects: Q Science
R Medicine
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Kidney Research UK (https://ror.org/02kx7se86)
National Institutes of Health (https://ror.org/01cwqze88)
Depositing User: Claire Peppiatt-Wildman
Date Deposited: 04 May 2023 08:21 UTC
Last Modified: 15 Sep 2023 10:23 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/101141 (The current URI for this page, for reference purposes)

University of Kent Author Information

Wildman, Scott S.P..

Creator's ORCID: https://orcid.org/0000-0003-4010-9791
CReDIT Contributor Roles:

Dunn, Kadeshia.

Creator's ORCID:
CReDIT Contributor Roles:

Kelley, Stephen P..

Creator's ORCID:
CReDIT Contributor Roles:

Lilley, Rebecca.

Creator's ORCID: https://orcid.org/0000-0002-9944-5944
CReDIT Contributor Roles:

Taylor, Kirsti D..

Creator's ORCID: https://orcid.org/0000-0003-4379-1095
CReDIT Contributor Roles:

Peppiatt-Wildman, Claire M..

Creator's ORCID: https://orcid.org/0000-0002-4406-8571
CReDIT Contributor Roles:
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