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.
Singh
A K
AK
Minnesota Veterinary Diagnostic Laboratories, Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul 55108, USA.
Jiang
Y
Y
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects*; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability; D005260:Female; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology; D007855:Lead Poisoning / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000032:analysis
D007295:Inositol Phosphates; D014316:Tritium; C081655:inositol-1,3,4,5-tetrakisphosphate; D012433:Ryanodine; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium