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Endothelin-3 decreases Ca2+ uptake in platelet membrane vesicles
M G Pernollet1, C Astarie-Dequeker, G Le Breton
1Department of Pharmacology, CNRS URA 1482, René Descartes University, Necker Medical School, Paris, France.
Journal of Cardiovascular Pharmacology
|January 1, 1995
Summary
Endothelin-3 (ET-3) inhibits calcium-ATPases in platelet dense tubules, reducing calcium uptake. This mechanism explains how ET-3 attenuates agonist-induced calcium release from internal stores.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Platelet activation involves intracellular calcium (Ca2+) mobilization.
- Endothelin-3 (ET-3) is known to modulate cellular responses, including Ca2+ signaling.
- The precise mechanism of ET-3's effect on internal Ca2+ stores is not fully elucidated.
Purpose of the Study:
- To investigate the mechanism by which endothelin-3 (ET-3) attenuates agonist-mediated Ca2+ mobilization.
- To determine ET-3's effect on Ca2+ uptake by platelet dense tubule Ca2+ pumps.
Main Methods:
- Studied 45Ca2+ uptake in platelet membrane vesicles.
- Compared effects of ET-3 and thapsigargin (Tg), a Ca2+ pump inhibitor.
- Assessed ATP-dependent and ATP-independent Ca2+ binding and accumulation.
Main Results:
- ET-3 dose-dependently reduced the rate and extent of ATP-dependent Ca2+ uptake.
- Thapsigargin inhibited both ATP-dependent and independent Ca2+ handling.
- ET-3 pretreatment partially attenuated Tg's inhibition of ATP-dependent Ca2+ uptake rate.
Conclusions:
- ET-3 is functionally coupled to dense tubule Ca2+-ATPases.
- ET-3 likely inhibits the catalytic cycle of Ca2+ pumps.
- This inhibition may deplete Ca2+ stores, reducing agonist-induced Ca2+ release.