Modulation by external Ca2+ and nicardipine of Ca2+ influx and cytosolic concentration in human erythrocytes.
Variations of Ca2+ influx (evaluated by the initial rate of 45Ca2+ uptake) and cytosolic free Ca2+ concentration ([Ca2+]i, measured with fura-2) were investigated in human erythrocytes. When external Ca2+ concentration ([Ca2+]o) rose from 1 to 2 mM, the initial rate of Ca2+ influx nearly doubled whereas [Ca2+]i increased only by 15%. Nicardipine dose-dependently decreased both initial rate of Ca2+ influx and [Ca2+]i (up to 53 and 18%. respectively at 10(-6) M). The less marked changes in [Ca2+]i than in Ca2+ influx indicate a partial adjustment of the Ca2+ extruding-pump activity to of Ca2+ influx. In vivo administration of nicardipine reduced [Ca2+]i only when its initial value exceeded 80 nM and prevented the rise in [Ca2+]i induced by the increase in [Ca2+]o. Our results indicate that nicardipine may reduce Ca2+ influx in human erythrocytes and participate in the control of [Ca2+]i when elevated.
David-Dufilho
M
M
Department of Pharmacology, CNRS 161670. Necker Medical School, Paris, France.
Astarie
C
C
Pernollet
M G
MG
Bergougnan
L
L
Comte
A
A
Dubray
C
C
Devynck
M A
MA
D002118:Calcium / Q000097:blood*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
D015220:Calcium Channels; D014638:Vanadates; D009529:Nicardipine; D002118:Calcium