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. IP1 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 receptors 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 IP1 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 Ca(2+)-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.