β-Adrenoceptor up-regulation and intracellular signal transduction systems

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In this research project, we attempted to investigate alterations in intracellular signal transduction systems coupling to β-adrenoceptors (β-AR) in association with β-AR up-regulationAt first, we confirmed that mouse cerebral cortical neurons in primary culture used had both β1- and β2-AR coupling to Camp generating system. Sustained exposure to nadolol induced a maximal increase of [3H] CGP-12177 binding after 6 hr of the exposure and increased both β-AR expressions on neuronal membrane. On the other hand, increased expression of mRNA of these eceptor was found 12 hr after the exposure. The increased receptor expression on neuronal membrane was due to increased translocation of receptor proteins from cytosol to membrane, and synthesis of receptor proteins did not participate in these events. After the expression of receptor mRNA increased, the expendent on synthesis of the proteinsIn association with β-AR up-regulation, forskolin-evoled formation of Camp increased. Among adenylate cyclase (AC) isozymes present in the neurons, only type I was found to increase significantly accompanying with β-AR up-regulation. In addition, β-AR up-regulation