Activation of the Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) and the Na(+)-Cl(-)-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine and serine residues, but the kinase pathways that mediate this action of vasopressin are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich kinase (SPAK) and oxidative stress responsive kinase (OSR1), can phosphorylate the cotransporters directly. In this process, a full-length SPAK variant and OSR1 interact with a truncated SPAK variant, which has inhibitory effects. Here, we tested whether SPAK is an essential component of the vasopressin stimulatory pathway. We administered desmopressin, a V2 receptor-specific agonist, to wild-type mice, SPAK-deficient mice, and vasopressin-deficient rats. Desmopressin induced regulatory changes in SPAK variants, but not in OSR1 to the same degree, and activated NKCC2 and NCC. Furthermore, desmopressin modulated both the full-length and truncated SPAK variants to interact with and phosphorylate NKCC2, whereas only full-length SPAK promoted the activation of NCC. In summary, these results suggest that SPAK mediates the effect of vasopressin on sodium reabsorption along the distal nephron.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582200 | PMC |
http://dx.doi.org/10.1681/ASN.2012040404 | DOI Listing |
Eur J Pharmacol
January 2025
Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Calcium/calmodulin dependent protein kinase II inhibitor 1 (Camk2n1) is closely associated with a peak logarithm of odds score in quantitative trait loci for systolic blood pressure. Increased Camk2n1 mRNA expression has been specifically observed in the kidneys of hypertension mouse models. However, the precise role of Camk2n1 in the kidney remains unclear.
View Article and Find Full Text PDFPlant Dis
December 2024
Department of Plant Protection, Biotechnical Faculty, University of Montenegro, 81000 Podgorica, Montenegro.
Am J Physiol Renal Physiol
December 2024
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, 14080 Mexico.
The field of the with no lysine kinases (WNKs) regulation of the thiazide-sensitive NaCl cotransporter (NCC) began at the start of the century with the discovery that mutations in two members of the family, WNK1 and WNK4, resulted in a condition known as Familiar Hyperkalemic Hypertension (FHHt). Since FHHt is the mirror image of Gitelman's syndrome that is caused by inactivating mutations of the SLC12A3 gene encoding NCC, it was expected that WNKs modulated NCC activity and that the increased function of the cotransporter is the pathophysiological mechanism of FFHt. This turned out to be the case.
View Article and Find Full Text PDFCNS Neurosci Ther
October 2024
Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Background: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus.
View Article and Find Full Text PDFPlants (Basel)
September 2024
Emeritus Faculty, Australian National University, Canberra 2601, Australia.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!