REGULATION OF PLASMA MEMBRANE-BOUND CA2+-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 Ca2+-ATPase pump. Our data show that 1,4,5-IP3 significantly (P < 0.005) stimulates Ca2+ transport, whereas 1,3,4,5-IP4 significantly (P < 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 Ca2+-ATPase pump.