We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Erythropoietin receptor-operated Ca<sup>2+</sup> channels: Activation by phospholipase C-γ1.
- Authors
Marrero, Mario B.; Venema, Richard C.; Ma, Heping; Ling, Brian N.; Eaton, Douglas C.
- Abstract
Erythropoietin receptor-operated Ca 2+ channels: Activation by phospholipase C-γ1. Erythropoietin (EPO) increases Ca2+ influx in vascular smooth muscle cells and acts both as a direct vasoconstrictor and vascular growth factor (that is, angiogenesis). However, the mechanism by which EPO promotes extracellular Ca2+ entry in contractile cells has not been elucidated. In hematopoietic cells, EPO induces tyrosine kinase (TK)-dependent activation of phospholipase C (PLC)-γ1 and Ca2+ influx via a voltage-independent Ca2+ conductance. In contractile mesangial cells, we have recently characterized a voltage-independent, 1 pS Ca2+ channel that is dependent on both TK and PLC-γ1 activity. Therefore, we examined cultured rat glomerular mesangial cells after timed exposure to recombinant human EPO (20 U/ml). Erythropoietin increased the tyrosine phosphorylation of PLC-γ1, promoted membrane complex formation between PLC-γ1 and the EPO receptor itself, and raised the levels of intracellular inositol 1,4,5-trisphosphate and intracellular Ca2+ . Consistent with our previous studies, 1 pS Ca2+ channel activity was extremely low under basal, unstimulated conditions in cell-attached patches, but was dramatically increased when EPO was present in the patch pipette. Tyrosine kinase inhibition with 100 μM genistein or 1 μM PP1 (Src; selective tyrosine kinase inhibitor) prevented all of these EPO-induced responses. We conclude that: (1 ) EPO-induced stimulation of 1 pS Ca2+ channels is mediated via a cytosolic Src TK in glomerular mesangial cells. (2 ) Stimulation of this Ca2+ -activated, Ca2+ -permeable channel is dependent on the tyrosine phosphorylation/activation of PLC-γ1. (3 ) This cascade provides a possible mechanism for the vasoconstriction and hypertension observed with clinical EPO use for the treatment of chronic...
- Publication
Kidney International, 1998, Vol 53, Issue 5, p1259
- ISSN
0085-2538
- Publication type
Academic Journal
- DOI
10.1046/j.1523-1755.1998.00887.x