PT - JOURNAL ARTICLE AU - M. A. OLESHANSKY AU - N. H. NEFF TI - Rat Pineal Adenosine Cyclic 3',5'-Monophosphate Phosphodiesterase Activity: Modulation <em>In Vivo</em> By a <em>Beta</em> Adrenergic Receptor DP - 1975 Sep 01 TA - Molecular Pharmacology PG - 552--557 VI - 11 IP - 5 4099 - http://molpharm.aspetjournals.org/content/11/5/552.short 4100 - http://molpharm.aspetjournals.org/content/11/5/552.full SO - Mol Pharmacol1975 Sep 01; 11 AB - Adenosine 3',5'-monophosphate (cAMP) phosphodiesterase of rat pineal gland shows characteristic high- and low-Km activities for cAMP. Treatment with l-isoproterenol (5 mg/kg intraperitoneally) increased the activity of the low-Km phosphodiesterase of pineal by 40% within 1 hr, and the activity returned to normal within 5 hr. The gain of activity was accompanied by a change in Vmax. Prior treatment of rats with dl-propranolol blocked the increase in phosphodiesterase activity while treatment with phentolamine did not, demonstrating modulation of enzyme activity through a beta adrenergic receptor. Activity was apparently induced at postsynaptic sites, as phosphodiesterase could still be increased by l-isoproterenol treatment after bilateral superior cervical ganglionectomy. Treatment of rats with cycloheximide prevented the response to l-isoproterenol, indicating that protein synthesis was required. Treatment with aminophylline, a phosphodiesterase inhibitor, produced a small but significant increase in the enzyme activity. Aminophylline in combination with a dose of l-isoproterenol below the threshold for phosphodiesterase activation resulted in greater activity than with aminophylline alone. These results suggest a direct relationship between cAMP concentrations and the increase in phosphodiesterase activity. Tolerance to repeated doses of beta receptor agonists might be explained by this mechanism. ACKNOWLEDGMENT We thank Mr. Jeffrey Rubenstein for his expert technical assistance.