JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Melvin, J. E.
Right arrow Articles by Baum, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Melvin, J. E.
Right arrow Articles by Baum, B. J.

Sympathetic denervation fails to produce beta adrenergic supersensitivity in adult rat parotid gland

JE Melvin, XJ He and BJ Baum

Clinical Investigations and Patient Care Branch, National Institute of Dental Research, Bethesda, Maryland.

Parotid acinar cells, prepared from pharmacologically sympathectomized adult rats (reserpine, 0.1 mg/kg/day for 1 week), display decreased responsiveness to beta adrenergic stimulation in vitro compared to cells from control and surgically sympathectomized rats. Both methods of denervation increase amylase content (amylase activity per microgram of DNA). Percent release of amylase activity and percent release of CCl3COOH-precipitable [14C]leucine were used as indicators of protein secretion. Exposure of cells from pharmacologically sympathectomized rats to the beta adrenergic agonist, isoproterenol, resulted in a marked reduction in receptor-coupled secretion (67% and 75% relative to controls, respectively). 8-Bromo-cyclic AMP, like isoproterenol, was unable to surmount this reserpine-induced inhibition of stimulated secretion, suggesting that an alteration in receptor-adenylate cyclase coupling is not responsible for the observed secretion defect. Cells prepared from surgically sympathectomized rats displayed modest decreases in stimulated secretion when the same secretory markers were monitored (30% and 25% relative to controls, respectively). The number of beta adrenoreceptors [( 3H]dihydroalprenolol binding sites) increased (35%), with no change in binding affinity, in membrane preparations from reserpine-treated rats. Thus, the observed inhibition of beta adrenergic agonist-induced secretion is not likely the result of alterations in beta adrenergic receptor characteristics. Short-term (1 week) surgical denervation had no effect on the number of beta adrenergic receptor sites; however, an increase in ligand binding affinity was noted. The decrease in the apparent Kd (30%) was not the result of a shift in receptor subtype as determined by competition studies with specific beta-1 (atenolol) and beta-2 (ICI 118,551) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 246, Issue 3, pp. 935-940, 09/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.