Metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate by the oocytes of Xenopus laevis.

The pathway and kinetics of inositol 1,4,5-trisphosphate (IP3) metabolism were measured in Xenopus laevis oocytes and cytoplasmic extracts of oocytes. Degradation of microinjected IP3 in intact oocytes was similar to that in the extracts containing comparable concentrations of IP3 ([IP3]). The rate and route of metabolism of IP3 depended on the [IP3] and the intracellular free Ca2+ concentration ([Ca2+]). At low [IP3] (100 nM) and high [Ca2+] (>/=1 microM), IP3 was metabolized predominantly by inositol 1,4, 5-trisphosphate 3-kinase (3-kinase) with a half-life of 60 s. As the [IP3] was increased, inositol polyphosphate 5-phosphatase (5-phosphatase) degraded progressively more IP3. At a [IP3] of 8 microM or greater, the dephosphorylation of IP3 was the dominant mode of IP3 removal irrespective of the [Ca2+]. At low [IP3] and low [Ca2+] (both </=400 nM), the activities of the 5-phosphatase and 3-kinase were comparable. The calculated range of action of IP3 in the oocyte was approximately 300 micron suggesting that IP3 acts as a global messenger in oocytes. In contrast to IP3, inositol 1,3,4, 5-tetrakisphosphate (IP4) was metabolized very slowly. The half-life of IP4 (100 nM) was 30 min and independent of the [Ca2+]. IP4 may act to sustain Ca2+ signals initiated by IP3. The half-life of both IP3 and IP4 in Xenopus oocytes was an order of magnitude or greater than that in small mammalian cells.