Emerging key roles for P2X receptors in the kidney

P2X ionotropic non-selective cation channels are expressed throughout the kidney and are activated in a paracrine or autocrine manner following the binding of extracellular ATP and related extracellular nucleotides. Whilst there is a wealth of literature describing a regulatory role of P2 receptors (P2R) in the kidney, there are significantly less data on the regulatory role of P2X receptors (P2XR) compared with that described for metabotropic P2Y. Much of the historical literature describing a role for P2XR in the kidney has focused heavily on the role of P2X1R in the autoregulation of renal blood flow. More recently, however, there has been a plethora of manuscripts providing compelling evidence for additional roles for P2XR in both kidney health and disease. This review summarizes the current evidence for the involvement of P2XR in the regulation of renal tubular and vascular function, and highlights the novel data describing their putative roles in regulating physiological and pathophysiological processes in the kidney

Current Perspective on the Location and Function of Gamma- Aminobutyric Acid (GABA) and its Metabolic Partners in the Kidney.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter located in the mammalian central nervous system, which binds to GABAA and GABAB receptors to mediate its neurological effects. In addition to its role in the CNS, an increasing number of publications have suggested that GABA might also play a role in the regulation of renal function. All three enzymes associated with GABA metabolism; glutamic acid decarboxylase, GABA ?-oxoglutarate transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) have been localised to the kidney providing the necessary machinery for localised GABA synthesis and metabolism. Moreover GABA receptors have been localised to both tubular and vascular structures in the kidney, and GABA is excreted in urine (~3 ?M) in humans. Despite the collective evidence describing the presence of a GABA system in the kidney, the precise function of such a system requires further clarification. Here we provide an overview of the current renal GABA literature and provide novel data that indicates GABA can act at contractile pericyte cells located along vasa recta capillaries in the renal medulla to potentially regulate medullary blood flow

Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important

The Persistence of White Privilege

Most discussions of white privilege emphasize the individual benefit to the holder of privilege. Yet dynamics beyond the individual combine to reinforce and reinvent white privilege. Socio-cultural factors operate in conjunction with material forces, enabling whites to self-perpetuate as a dominant racialized identity. Material forces such as the distribution of societal goods and resources, the division of labor, and immigration policies, create a world that privileges whiteness. Socio-cultural factors, including discursive practices, patterns of behavior, and the thinking patterns that language creates, further strengthen white privilege, contributing to its endurance. This article focuses on four socio-cultural factors that reinforce white privilege: (1) the contemporary cultural push to colorblindness; (2) the sleight of mind that typifies the relation between an individual and groups in American culture; (3) a comfort zone in whiteness, which includes whiteness as the fabric of daily life for whites and white participation in the construction of race from a white-privileged viewpoint; and (4) the tendency for holders of white privilege to take back the center in discourse, turning attention away from potentially uncomfortable conversations about race toward an emphasis on white concerns and issues. The article concludes by considering the relevance of privilege to law, demonstrating how an analysis of privilege would illuminate legal facts patterns and further social justice

Democracy and Social Justice: Founding Centers for Social Justice in Law Schools

Protecting democracy by combating inequality is the task of social justice lawyers. The practice of democracy mandates inclusion of the diverse populations of this nation into the social order. Social justice lawyers seek to give material meaning to democratic ideals in the daily lives of individuals and communities that are marginalized, subordinated, and underrepresented. Currently, not enough lawyers serve the disenfranchised and not enough lawyers emerge from disenfranchised communities. Hence, the disenfranchised continue to be denied access to legal resources, to the detriment of democracy. Legal educators must begin to think about how to institutionalize consciousness about social justice as part of the canon of legal education and to promote the idea that a professional is one dedicated to public service and the provision of justice. The creation of centers and institutes in social justice law can help accomplish this goal. This article discusses the institutional values necessary for building a successful center, emphasizing communication and inclusion. It also addresses key components of a successful social justice program, including a curriculum that coordinates theory with practice in the traditional classroom and clinical settings; faculty scholarship and related social justice practice; involvement of students, student groups, and staff; an intellectual climate that promotes extracurricular events and work with other centers of specialization within the law school and university; and alumni/community relations and fundraising. The article makes suggestions for how to implement each element

Revisiting Privilege Revealed and Reflecting on Teaching and Learning Together

In 1996, Professor Stephanie M. Wildman co-authored Privilege Revealed: How Invisible Preference Undermines America, a book offering differing perspectives on how various privileges arise and how society needs to become aware of the invisible privileges in everyday life. In this article, Professor Wildman revisits Privilege Revealed and addresses why teaching about privilege is important and the value in learning about systemic privilege. She provides student reflections on studying privilege to highlight that everyone needs knowledge to make privilege visible and to combat its operation. Professor Wildman argues that a society which urges people to be colorblind is counter to the idea of mindfulness, as people need to understand the role race plays in society. Professor Wildman offers the notion that ‘color insight’ better serves the goals of racial equality and justice. Applying color insight utilizes four steps: (1) considering context for any discussion about race; (2) examining systems of privilege; (3) unmasking perspectivelessness and white normativeness; and (4) combating stereotyping and looking for the ‘me’ in each individual. Professor Wildman concludes that mindfulness of other people’s oppression offers a positive response to privilege, enabling the holder to use that privilege as a step toward social justice

Hearing Women: From Professor Hill to Dr. Ford

(Excerpt) One of the recent traumas, another skirmish in today’s civilian conflict over what kind of society America will be, arose from Dr. Christine Blasey Ford’s testimony about sexual assault she had endured. Her composed, measured statement during the nowJustice Brett Kavanaugh confirmation hearing exemplified bravery in the face of adversity. The Senate and the nation’s response to her testimony underscored the high stakes in the ongoing ideological conflict, beyond the obvious prize of a Supreme Court seat. Constituents in the current ideological battle had differing reactions to Ford’s testimony and to this hearing, reflecting a range of views about a number of topics, including civility, sexual assault, and the criminal justice system

The Dream of Diversity and the Cycle of Exclusion

The racial transformation of society envisioned in Martin Luther King\u27s dream has been an emotional and powerful ideal. That vision has gone through its own transformation: it was first described as integration, then affirmative action, and then diversity and multiculturalism. As each of these phrases acquired negative connotation from reactionary, conservative backlashes, a new phrase has had to be invented to carry forward that transformative vision. Yet the cycle of exclusion that gives privileges to the dominant cultural status quo continues