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Effects of Lead on Adenylate Cyclase Activity in Rat Cerebral Cortex

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Abstract

Lead decreased in a dose dependent manner the basal AC activity in membranes of rat cerebral cortex (IC50 = 2.5 ± 0.1 μM). In membranes preincubated under basal conditions, AC activity was stimulated by approximately two and fourfold by 10 μM Gpp(NH)p or forskolin, respectively. Under basal conditions, lead (3 μM) inhibited enzyme activity up to 50%, but was not able to inhibit the Gpp(NH)p- or the forskolin-stimulated AC activity. However, in membranes preincubated with Gpp(NH)p (10 μM), lead (3 μM) had no significant effect on enzyme activity, but it partly blocked the stimulation of AC activity elicited by forskolin (10 μM). In membranes preincubated with 10 μM lead, the addition of 10 μM Gpp(NH)p or forskolin in the incubation medium did not stimulate AC activity. However, when added together in the incubation medium Gpp(NH)p + forskolin produced an increase in enzyme activity. In membranes preincubated with 10 μM lead + 10 μM Gpp(NH)p, Gpp(NH)p (10 μM) or forskolin (10 μM) added alone or in combination to the incubation medium did not stimulate AC activity. Moreover, under these latter conditions lead had no further effect on enzyme activity. These results indicate that lead may interact with G-proteins and with the catalytic subunit of cerebral cortical AC to produce inhibition of the enzyme activity.

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Authors and Affiliations

  1. Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900-, Florianópolis, SC, Brazil

    Ana Lúcia S. Rodrigues

  2. Department of Biochemistry, Institute of Basic Science of Health, Federal University of Rio Grande do Sul, 90046-900-, Porto Alegre, RS, Brazil

    Andrea Regner & Diogo O. Souza

  3. Department of Chemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, 97119-900-, Santa Maria, RS, Brazil

    Maribel A. Rubin

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  1. Ana Lúcia S. Rodrigues
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Rodrigues, A.L.S., Regner, A., Rubin, M.A. et al. Effects of Lead on Adenylate Cyclase Activity in Rat Cerebral Cortex. Neurochem Res 24, 1037–1042 (1999). https://doi.org/10.1023/A:1021008910900

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