TY - JOUR
T1 - PTH and DA regulate Na-K ATPase through divergent pathways
AU - Khundmiri, Syed Jalal
AU - Lederer, Eleanor
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Parathyroid hormone (PTH) and dopamine (DA) inhibit Na-K ATPase activity and sodium-phosphate cotransport in proximal tubular cells. We previously showed that PTH and DA inhibit phosphate transport in opossum kidney (OK) cells through different signaling pathways. Therefore, we hypothesized that PTH and DA also inhibit Na-K ATPase through divergent pathways. We measured PTH and DA inhibition of Na-K ATPase activity in the presence of inhibitors of signaling pathways. PTH and DA inhibited Na-K ATPase in a biphasic manner, the early inhibition through protein kinase C (PKC)- and phospholipase A2 (PLA2)-dependent pathways and the late inhibition through protein kinase A- and PLA2-dependent pathways. Inhibition of extracellular signal-regulated kinase (ERK) activation blocked early and late inhibition of Na-K ATPase by PTH but not by DA. Pertussis toxin blocked early and late inhibition by DA but not by PTH. Treatment with DA, but not PTH, resulted in an early downregulation of basolateral membrane expression of the a-subunit, whereas total cellular expression remained constant for both agonists. We conclude that PTH and DA regulate Na-K ATPase by different mechanisms through activation of divergent pathways.
AB - Parathyroid hormone (PTH) and dopamine (DA) inhibit Na-K ATPase activity and sodium-phosphate cotransport in proximal tubular cells. We previously showed that PTH and DA inhibit phosphate transport in opossum kidney (OK) cells through different signaling pathways. Therefore, we hypothesized that PTH and DA also inhibit Na-K ATPase through divergent pathways. We measured PTH and DA inhibition of Na-K ATPase activity in the presence of inhibitors of signaling pathways. PTH and DA inhibited Na-K ATPase in a biphasic manner, the early inhibition through protein kinase C (PKC)- and phospholipase A2 (PLA2)-dependent pathways and the late inhibition through protein kinase A- and PLA2-dependent pathways. Inhibition of extracellular signal-regulated kinase (ERK) activation blocked early and late inhibition of Na-K ATPase by PTH but not by DA. Pertussis toxin blocked early and late inhibition by DA but not by PTH. Treatment with DA, but not PTH, resulted in an early downregulation of basolateral membrane expression of the a-subunit, whereas total cellular expression remained constant for both agonists. We conclude that PTH and DA regulate Na-K ATPase by different mechanisms through activation of divergent pathways.
KW - Extracellular signal-regulated kinase
KW - Opossum kidney cells
KW - Phospholipase A
KW - Protein kinase A
KW - Protein kinase C
UR - http://www.scopus.com/inward/record.url?scp=0036084220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036084220&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00111.2000
DO - 10.1152/ajprenal.00111.2000
M3 - Article
C2 - 11832434
AN - SCOPUS:0036084220
VL - 282
SP - F512-F522
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3 51-3
ER -