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Vol. 281, Issue 2, 965-971, 1997
Department of Pharmacology, University of Colorado Health Sciences
Center Denver, Colorado (T.J.G., P.C.B.) and
Department of Veterans
Affairs Medical Center, Research Service, Denver, Colorado (P.C.B.)
Localization of age-related deficits in the cerebellar
beta adrenergic signal transduction cascade were
investigated electrophysiologically using forskolin (FORSK) and
adenosine-3
,5
-cyclic monophosphothioate Sp-isomer (Sp-cAMPS) applied
via pressure ejection from extracellular multibarreled
glass electrodes to activate the transduction cascade. In young rats,
100 µM FORSK activated AC, and 100 µM Sp-cAMPS activated protein
kinase A; thus, both increased GABAergic inhibition of Purkinje cell
firing. In aged rats, however, 100 µM FORSK was unable to increase
GABAergic inhibition of Purkinje cell firing. In addition, 1 mM
7
-decacetyl-7
-(
-N-methylpiperazino)butyryl-forskolin, an
analog of FORSK, was also unable to increase GABAergic inhibition in
aged rats. In contrast, Sp-cAMPS was able to increase GABAergic inhibition in aged rats, but higher doses were required than in young
rats. Isoproterenol (ISO), a beta adrenergic agonist,
was ineffective in increasing GABAergic inhibition of Purkinje firing in aged rats when tested alone, but ISO was effective in increasing Purkinje cell inhibition when ISO was tested with Sp-cAMPS. The results
of this experiment indicate that one age-related deficit in the
cerebellar beta adrenergic system occurs at the level of protein kinase A activation.
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