Comparative effects of age and chronic low-level lead exposure on calcium mobilization from intracellular calcium stores in brain samples obtained from the neonatal and the adult rats

The effects of age and chronic low-level lead exposure were studied on (a) [³H]IP₃ and [³H]Ry binding to their respective receptors in brain membranes and (b) Ca²⁺ release from internal Ca²⁺ stores in brain synaptosomes obtained from the neonatal and adult rats. [³H]IP₃ and [³H]Ry binding sites in the control-adult membranes were greater than those in the control-neonatal membranes. [³H]IP₃ bound to a single high-affinity site, IP₃-R. Ca²⁺ decreased [³H]IP₃ binding to its receptor. [³H]Ry bound to at least four subspecies of Ry-Rs. KCl and IP₃ increased, but Ca²⁺ caused a biphasic affect on [³H]Ry binding in brain membranes. IP₃ and caffeine both caused greater increase in [Ca²⁺](i) in the adult synaptosomes than the neonatal synaptosomes. IP₄ redistributed Ca²⁺ from the caffeine- sensitive pool to the IP₃-sensitive pool. IP₃ increased the caffeine- induced mobilization of Ca²⁺ in synaptosomes. Chronic low-level lead exposure decreased the binding of [³H]IP₃ to its receptor in membranes, attenuated the IP₃-induced Ca²⁺ mobilization in synaptosomes, abolished the IP₄-induced redistribution of Ca²⁺ from Ry sensitive Ca²⁺ store to IP₃-sensitive Ca²⁺ store, and attenuated the effects of IP₃ on [Ca²⁺](i) in caffeine stimulated synaptosomes. Lead exposure, however, did not affect [³H]Ry binding to Ry-R in membranes or the caffeine-induced increase in [Ca²⁺](i) in synaptosomes. Chronic lead exposure protected IP₃-R against Ca²⁺-induced inhibition in membranes. This protection was greater in the neonatal samples than the adult samples. This suggests that chronic low-level lead exposure down-regulated the IP₃-induced Ca²⁺ mobilization in synaptosomes without effecting the caffeine-induced Ca²⁺ mobilization.