ELSEVIER Toxicology Letters 87 (!596) I I - 17 Toxicology Letters In vitro and in vivo effects of lead, methyl mercury and mercury on inositol 1,4,5trisphosphate and 1,3,4,5- tetrakisphosphate receptor bindings in rat brain Chellu S. Chettya, Sharada Rajannab, Elizabeth Hall”, Prabhakara R. Yallapragadac”, Bettaiya Rajanna*d “Department of Biology, Savannah State College, Savannah, GA, USA bDeportment of Mathematics and Computer Science, Alcom State University, Lorman. MS, USA cDivision of Natural Sciences, Selma University, Sehna, AL, USA dDepartment ar Biological Sciences, loo0 ASU Drive, Box 870, Alcorn Slate University, Lannan, MS 39096, USA Received 1 November 1995; revised 15 March 1996; accepted 19 March 1996 zyxwvutsrqponmlkjihgfedcbaZY Ab6hCt In vitro and in viva effects of mercury (Hg), methyl mercury (MM) and lead (Pb) on [3H]inositol 1,4,5- trisphosphate (IP,) and [3H]inositol 1,3,4,5tetrakisphosphate (IP,) receptor binding in the Sprague-Dawley rat brain cerebellar membranes were studied. In vitro studies indicate that binding of [‘H]IP, and [3H]IP4 to cerebellar mem- branes was inhibited by Hg while they were stimulated by MM or Pb in a concentration-dependent manner. MM was more potent (ECSo 3.4 PM) than Pb (EC,, 18.2 PM) in stimulating the [‘H]IP, receptor binding activity whereas Pb (ICw, 30 PM) was more potent than MM (I&, 133 PM) in stimulating the [‘HJIP, receptor binding. When the rats were treated (i.p) with Hg (5 mg/kg body wt.) or MM (5 mg/kg body wt.) or Pb (25 mg&g body wt.) for 3 or 24 h, no significant alteratilonsin [3H]IP3 receptor binding were observed in cerebellum and cerebral cortex. But the above treatment of Pb or MM for 3 or 24 h to rats resulted in an increase of [3H]IP4 receptor binding in the membranes of cerebral cortex. However, the rats treated with Hg (1 mg/kg body wt./day) or Pb (25 mg/kg body wt./day) for 7 days did not show any alteration in binding of [3H]IP3 to its receptors in cerebellar membranes but an increase in this receptor binding was noticed with the treatment of MM (2.5 mg/kg body wt./day) for 7 days. The cerebellum and cerebral cortex of rats with the above treatment of MM or Pb for 7 days exhibited an increase in [%]IP, receptor binding. These in vitro and in vivo data suggest that alterations in inositol polyphosphate receptor binding by metals could result in alterations in intracellular calcium levels which may influence neuronal activity. Keywordr: Heavy metals; Inositol polyphosphates; Calcium homeostasis; Rat brain zyxwvutsrqponmlkjihgfedcbaZYXWV 1. Introduelion Heavy metals have been shown to affect the release of neurotransmitters and activity of AT- l Corresponding author. ’ Current address: Department of Zoology, Andhra Univer- sity, Waltair-53403, India. Pases that are involved in the regulation of calcium fluxes [ 1,2]. Several biological aberrations produc- ed by lead (Pb) are related to its ability to either inhibit or mimic the action of Ca2+ [3,4]. In recent years, it has been shown that a variety of com- pounds such as neurotransmitters, neuropeptides, hormones and growth factors interact with specific 0378-4274/9~Y$15.00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PII: SO378-4274(96)031670-3