Impairment of adenylyl cyclase 2 function and expression in hypoxanthine phosphoribosyltransferase-deficient rat B103 neuroblastoma cells as model for Lesch-Nyhan disease: BODIPY-forskolin as pharmacological tool.

Naunyn-Schmiedeberg's Archives of Pharmacology
Liz KinastRoland Seifert

Abstract

Hypoxanthine phosphoribosyl transferase (HPRT) deficiency results in Lesch-Nyhan disease (LND). The link between the HPRT defect and the self-injurious behavior in LND is still unknown. HPRT-deficient rat B103 neuroblastoma cells serve as a model system for LND. In B103 cell membranes, HPRT deficiency is associated with a decrease of basal and guanosine triphosphate-stimulated adenylyl cyclase (AC) activity (Pinto and Seifert, J Neurochem 96:454-459, 2006). Since recombinant AC2 possesses a high basal activity, we tested the hypothesis that AC2 function and expression is impaired in HPRT deficiency. We examined AC regulation in B103 cell membranes, cAMP accumulation in intact B103 cells, AC isoform expression, and performed morphological studies. As most important pharmacological tool, we used 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene forskolin (BODIPY-FS) that inhibits recombinant AC2 but activates ACs 1 and 5 (Erdorf et al., Biochem Pharmacol 82:1673-1681, 2011). In B103 control membranes, BODIPY-FS reduced catalysis, but in HPRT(-) membranes, BODIPY-FS was rather stimulatory. 2'(3')-O-(N-methylanthraniloyl) (MANT)-nucleoside 5'-[γ-thio]triphosphates inhibit recombinant ACs 1 and 5 more potently than AC2. In B103 control mem...Continue Reading

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Citations

Jun 13, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Roland Seifert
Jun 13, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Martina B Michel-Reher, Martin C Michel
Mar 15, 2015·Molecular Genetics and Metabolism·Eric B DammerH A Jinnah
Aug 12, 2014·Biochemical and Biophysical Research Communications·Ulrike BeckertRoland Seifert
Dec 5, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·Erich H Schneider, Roland Seifert
May 26, 2016·Naunyn-Schmiedeberg's Archives of Pharmacology·Roland Seifert
Oct 27, 2021·Physiological Reviews·Katrina F OstromRennolds S Ostrom

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