INFLUENCE OF PROBES FOR CALCIUM-CALMODULIN AND PROTEIN-KINASE-C SIGNALING ON THE PLASMA-MEMBRANE CA2-ATPASE ACTIVITY OF RAT SYNAPTOSOMES AND LEUKOCYTE MEMBRANES()
N. Grosman, INFLUENCE OF PROBES FOR CALCIUM-CALMODULIN AND PROTEIN-KINASE-C SIGNALING ON THE PLASMA-MEMBRANE CA2-ATPASE ACTIVITY OF RAT SYNAPTOSOMES AND LEUKOCYTE MEMBRANES(), Immunopharmacology, 40(2), 1998, pp. 163-171
The influence of selected inhibitors of calcium signalling on the plas
ma membrane Ca2+-ATPase activity of rat synaptosomes and peritoneal le
ukocyte membranes was studied. The calmodulin inhibitor calmidazolium
was an efficient inhibitor (50%) of the synaptosomal Ca2+-ATPase activ
ity in a manner competitive with phosphatidylserine. The inhibition by
CGS 9343B (30%) was not counteracted by phosphatidylserine. The intra
cellular calcium antagonist TMB-8 and the protein kinase inhibitor sta
urosporine and the derivatives CGP 41251 and CGP 42700 hardly affected
the synaptosomal Ca2+-ATPase activity. The flavonoid quercetin was a
more effective inhibitor of the ATPase activity of synaptosomal than o
f leukocyte membranes. Phloretin, at relatively high concentrations, c
aused only a modest inhibition of synaptosomes. The protein kinase C i
nhibitor sphingosine was a weak inhibitor of the synaptosomal but an e
ffective inhibitor of the leukocyte membrane Ca2+-ATPase activity. The
antineoplastic ether phospholipids BM 41.440 (ilmofosine) and ET-18-O
CH3 (edelfosine) effectively inhibited the leukocyte membranes whereas
the ATPase activity of synaptosomes was significantly increased by 20
mu M and slightly inhibited by higher concentrations of these agents.
The analogue hexadecylphosphocholine (miltefosine) did not affect the
ATPase activity of the synaptosomes and only inhibited that of the le
ukocyte membranes at concentrations above 20 mu M. These results show
that several test substances of current interest affect the activity o
f the plasma membrane Ca2+-ATPase. The effects depend on the origin of
the membranes. The investigation does not permit a distinction betwee
n direct effects on the enzyme and an interference with its membrane e
nvironment although the latter is indicated for the ether phospholipid
s. (C) 1998 Elsevier Science B.V. All rights reserved.