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

Abstract

The effects of age and chronic low-level lead exposure were studied on (a) [ 3H]IP 3 and [ 3H]Ry binding to their respective receptors in brain membranes and (b) Ca 2+ release from internal Ca 2+ stores in brain synaptosomes obtained from the neonatal and adult rats. [ 3H]IP 3 and [ 3H]Ry binding sites in the control-adult membranes were greater than those in the control-neonatal membranes. [ 3H]IP 3 bound to a single high-affinity site, IP 3-R. Ca 2+ decreased [ 3H]IP 3 binding to its receptor. [ 3H]Ry bound to at least four subspecies of Ry-Rs. KCl and IP 3 increased, but Ca 2+ caused a biphasic affect on [ 3H]Ry binding in brain membranes. IP 3 and caffeine both caused greater increase in [Ca 2+] I in the adult synaptosomes than the neonatal synaptosomes. IP 4 redistributed Ca 2+ from the caffeine-sensitive pool to the IP 3-sensitive pool. IP 3 increased the caffeine-induced mobilization of Ca 2+ in synaptosomes. Chronic low-level lead exposure decreased the binding of [ 3H]IP 3 to its receptors in membranes, attenuated the IP 3-induced Ca 2+ mobilization in synaptosomes, abolished the IP 4-induced redistribution of Ca 2+ from Ry sensitive Ca 2+ store to IP 3-sensitive Ca 2+ store, and attenuated the effects of IP 3 on [Ca 2+] 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 [Ca 2+] I in synaptosomes. Chronic lead exposure protected IP 3-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 IP 3-induced Ca 2+ mobilization in synaptosomes without effecting the caffeine-induced Ca 2+ mobilization.