Alteration of Ca2+ fluxes in brain microsomes by K+ and Na+: modulation by sulfated polysaccharides and trifluoperazine.
Rat brain microsomes accumulate Ca2+ at the expense of ATP hydrolysis. The rate of transport is not modulated by the monovalent cations K+, Na+, or Li+. Both the Ca2+ uptake and the Ca(2+)-dependent ATPase activity of microsomes are inhibited by the sulfated polysaccharides heparin, fucosylated chondroitin sulfate, and dextran sulfate. Half-maximal inhibition is observed with sulfated polysaccharide concentrations ranging from 0.5 to 8.0 micrograms/ml. The inhibition is antagonized by KCl and NaCl but not by LiCl. As a result, Ca2+ transport by the native vesicles, which in the absence of polysaccharides is not modulated by monovalent cations, becomes highly sensitive to these ions. Trifluoperazine has a dual effect on the Ca2+ pump of brain microsomes. At low concentrations (20-80 microM) it stimulates the rate of Ca2+ influx, and at concentrations > 100 microM if inhibits both the Ca2+ uptake and the ATPase activity. The activation observed at low trifluoperazine concentrations is specific for the brain Ca(2+)-ATPase; for the Ca(2+)-ATPases found in blood platelets and in the sarcoplasmic reticulum of skeletal muscle, trifluoperazine causes only a concentration-dependent inhibition of Ca2+ uptake. Passive Ca2+ efflux from brain microsomes preloaded with Ca2+ is increased by trifluoperazine (50-150 microM), and this effect is potentiated by heparin (10 micrograms/ml), even in the presence of KCl. It is proposed that the Ca(2+)-ATPase isoforms from brain microsomes is modulated differently by polysaccharides and trifluoperazine when compared with skeletal muscle and platelet isoforms.
Rocha
J B
JB
Departamento de Química, Universidade Federal de Santa Maria, Brazil.
Wolosker
H
H
Souza
D O
DO
de Meis
L
L
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006493:Heparin / Q000494:pharmacology; D007477:Ions; D007527:Isoenzymes / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D012964:Sodium / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology*
D007477:Ions; D007527:Isoenzymes; D011134:Polysaccharides; D014268:Trifluoperazine; D006493:Heparin; D012964:Sodium; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium