Renal intercalated cells and blood pressure regulation

Abstract

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl− absorption and HCO3− secretion largely through pendrin-dependent Cl−/HCO3− exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl− absorption, but also by modulating the aldosterone response for epithelial Na+ channel (ENaC)-mediated Na+ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

Sex-dependent differences in water homeostasis in wild-type and V-ATPase B1-subunit deficient mice

“…In addition to the better-understood role of collecting duct principal cells in volume regulation, it is becoming increasingly apparent that the adjacent intercalated cells (ICs) also participate in regulating body fluid balance, mostly via Na + and Cl - transport [9–11], and through a paracrine mechanism via secreted prostaglandin E2 [12, 13]. The goal of the current study was to establish if there is any difference in the water balance between male and female mice under baseline conditions and to determine whether this involves IC function by using Atp6v1b1null mice that lack a critical subunit of the vacuolar proton-pumping ATPase (V-ATPase) that partially disrupts IC function.…”

Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis

“…5 The ICs are responsible for pH homeostasis, protection against bacterial infection of the urinary system, 6 and express carbonic anhydrases, vacuolar H + -ATPase pumps, and anion exchangers (AEs). [7][8][9] On the basis of the differential localization of vacuolar H + -ATPase and the type and localization of AEs (apical versus basolateral), ICs are classified into type A, B, or non-A-non-B [10][11][12][13][14] ICs that belong to an evolutionarily conserved cell type referred to as proton-secreting cells or ionocytes 15 found in many mammalian organ systems, including the connecting segment and collecting ducts of kidneys, inner ear, and epididymis. The differentiation of proton-secreting cells in Xenopus and zebrafish skins and the mammalian kidney collecting ducts is promoted by Foxi1 orthologs, and negatively regulated by Notch signaling.…”

Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells

“…21,58,65,66 Angiotensin II and aldosterone stimulate V-ATPase in A-ICs, thus increasing luminal H + secretion, whereas aldosterone additionally induces pendrin in B-ICs, which facilitates the function of the epithelial sodium channel in PCs. [65][66][67][68][69] The AVP-dependent modulation of RAAS may take place at the level of hypothalamus via stimulation of adrenocorticotropic hormone release as reported in rats. 70 In mice, effects of AVP on RAAS may additionally be mediated by V1aR in MD cells, because V1aR-deficient mice exhibited hyporeninemia and low BP.…”