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Molecular Pharmacology, Vol 11, 552-557, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Rat Pineal Adenosine Cyclic 3',5'-Monophosphate Phosphodiesterase Activity: Modulation In Vivo By a Beta Adrenergic Receptor

M. A. OLESHANSKY 1 and N. H. NEFF 1

1 Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032

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.

Note:
ACKNOWLEDGMENT We thank Mr. Jeffrey Rubenstein for his expert technical assistance.

Submitted on March 3, 1975




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K. Minneman and L. Iversen
Cholera toxin induces pineal enzymes in culture
Science, May 21, 1976; 192(4241): 803 - 805.
[Abstract] [PDF]


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