737-743Inositol 1,4,5-trisphosphatee (IP3), an intracellular
messenger, releases Ca2+ from microsomes. Ca2+ plays a
major role in regulating various cellular events like neural transmission and
regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury
(Hg) were reported to alter Ca2+-regulated events thereby causing
neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca2+
release from rat brain microsomes under the influence of Al, Pb and Hg.
Different concentrations of metals were tested over a designated time scale and
their effects on IP3 mediated Ca2+ release from microsomes were
monitored using Fura-2 technique. All the three metals inhibited IP3 mediated
Ca2+ release, Pb being more potent. The order of potency of these
three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently
released Ca2+ from microsomes. Re-uptake of Ca2+ into
microsomes was inhibited by all the three metals, Pb being more potent.
Microsomal Ca2+-ATPase activity was also inhibited by all the three
metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may
be due to the interference of these metals with IP3 mediated calcium release
and also interfering with the microsomal Ca2+ sequestration
mechanism. Differential effects of heavy metal induced changes in
Ca2+ flux can be used as an index of relative toxicity