Regulation of plasma membrane-bound Ca(2+)-ATPase pump by inositol phosphates in rat brain.
We have previously shown that inositol 1,4,5-trisphosphate (1,4,5-IP3) may participate in signal transduction in brain by inhibiting plasma membrane-bound Na(+)-Ca2+ exchanger. This study was therefore designed to determine whether 1,4,5-IP3 and/or inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) might also affect Ca2+ transport by the plasma membrane Ca(2+)-ATPase pump. Our data show that 1,4,5-IP3 significantly (P less than 0.005) stimulates Ca2+ transport, whereas 1,3,4,5-IP4 significantly (P less than 0.006) inhibits transport by the pump. However, in the presence of both 1,4,5-IP3 and 1,3,4,5-IP4, the stimulatory effect of 1,4,5-IP3 is dominant. Thus Ca2+ transport was significantly stimulated as though 1,4,5-IP3 alone was present. We also observed that 1,3,4-IP3, which had no effect on Ca2+ transport by itself, antagonizes the stimulatory action of 1,4,5-IP3 and potentiates the inhibition of Ca2+ transport by 1,3,4,5-IP4. Half-maximal activities were observed at 10(-8) M. Our data suggest that 1,3,4,5-IP4, 1,4,5-IP3, and 1,3,4-IP3 may participate in signal transduction in brain by regulating the plasma membrane-bound Ca(2+)-ATPase pump.
Fraser
C L
CL
Department of Medicine, Veterans Affairs Medical Center, San Francisco, California 94121.
Sarnacki
P
P
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000494:pharmacology*; D007700:Kinetics; D051381:Rats; D013572:Synaptic Vesicles / Q000187:drug effects / Q000201:enzymology*
D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002122:Calcium Chloride; D002118:Calcium