Functional relationship between β-adrenergic receptor up-regulation and adenylate cyclase expression in mouse cerebral cortical neurons *
The functional relationship between β -adrenergic rcccptors (β -AR) and adenylate cyclase (AC) expression following long-term exposure to nadolol, a non-selective β-AR antagonist, was examined using primary cultures of mouse cerebral cortical neurons. Increase in [3 H]CGP12177 binding to particulate fractions from the neurons was dependent on the concentration of nadolol and the duration of exposure to it. Scatchard analysis revealed that the increase in [3 H]CGP12177 binding following the exposure to 10-8 M nadolol for five days was due to a significant increase in the Bmax value. In addition, under the above conditions, both B1-and /B2-AR were found to have been up-regulated when examined by the [3H]CGP12177 binding assay and Northern blot analysis, indicating that the up-regulation of β -AR is a consequence of β -AR protein synthesis. Cyclic AMP (cAMP) formation stimulated by isoproterenol and forskolin was enhanced after exposure to 10-8 M nadolol for more than 72 and 24 hr, respectively. After exposure to 10-8 M nadolol. Northern and Western blot analyses for AC showed increased expression of AC type I whereas, other types of AC ; i.e.) types II, VIII, and IX, were unchanged in. These results indicate that continuous exposure to nadolol up-regulated β-AR with increase its mRNA expression and cAMP formation activity due to increase in AC type I expression. (Accepted on March 7 , 2001) Kawasaki Igakkaishi 27(2 ) 97 -110, 2001
