Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 39
Identification of suramin as a direct inhibitor of adenylyl cyclase and a competitive
inhibitor of [3H]-forskolin binding
Jiri Novotny, Jiri Stöhr, Lenka Bourova and Petr Svoboda
Department of Biochemistry of Membrane Receptors, Institute of Physiology, Academy
of Sciences, Videnska 1083, Prague 4 and Department of Physiology, Faculty of Natural
Sciences, Charles University, Vinicna 7, 120 00 Prague 2, Czech Republic
E-mail: novjiri@biomed.cas.cz
Activity of adenylyl cyclase (AC) is markedly higher in brain cortex from young than from
adult rats. Here we compared the modulatory effects of many different compounds on AC
activity in cerebrocortical preparations from young (12-day-old) and adult (90-day-old) rats.
We did not found any substantial difference between the effects of all tested agents and AC
activity measured in various conditions was always about two-fold higher in samples from
young animals. Our experiments analysing the presumed modulatory role of suramin revealed
that this pharmacologically important drug may act as a direct inhibitor of AC. The enzyme
activity was diminished to the same extent by suramin in membranes from both tested age
groups. Moreover, suramin was able to reduce AC activity stimulated by Mn2+ or forskolin
in membranes derived from S49 cyc- cells lacking Gs-alpha protein. We also determined
characteristics of [3H]-forskolin binding in cerebrocortical membranes and these
measurements allowed us to detect high-affinity, as well as super-high-affinity, [3H]forskolin
binding sites. The binding parameters of these sites differed quite significantly in
samples from both age groups tested. We also assessed the potential effect of suramin and
results of these analyses suggested that this compound may act as a potent competitive
inhibitor of [3H]-forskolin binding. In summary, our present studies extend the existing array
of suramin cellular tagets by identifiying this drug as a potent direct inhibitor of AC and [3H]forskolin
binding.
This investigation was supported by Centrum of Neuroscience (LC 554).
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