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Desipramine desensitizes beta-adrenergic signal transduction in salivary glands: differential regulation with age.

Authors
  • Scarpace, P J
  • Koller, M M
  • Rajakumar, G
Type
Published Article
Journal
European Journal of Pharmacology
Publisher
Elsevier
Publication Date
Sep 15, 1993
Volume
247
Issue
1
Pages
65–72
Identifiers
PMID: 8258362
Source
Medline
License
Unknown

Abstract

We previously reported that the tricyclic antidepressant, desipramine desensitizes beta-adrenergic signal transduction in parotid and submandibular salivary glands. To determine the consequences of repeated desipramine administration on beta-adrenergic signal transduction in salivary glands from aged rats and whether the recovery after drug withdrawal is impaired, we assessed the effects of 28-day desipramine administration and the reversibility of this treatment following a 15-day washout period on beta-adrenoceptors and adenylyl cyclase activity in parotid and submandibular glands from F-344 rats of 6, 12 and 24 months of age. beta-Adrenoceptors were also assessed in the cerebral cortex. Desipramine administration down-regulated receptor number and attenuated isoproterenol-stimulated adenylyl cyclase activity in all three ages of rats. However, the reduction in isoproterenol-stimulated adenylyl cyclase activity was greater than the loss of receptor number. Desipramine administration attenuated the efficacy of NaF-stimulated activity with no change in forskolin-stimulated adenylyl cyclase activity. These data suggest that in addition to desensitizing beta-adrenergic-mediated signal transduction, desipramine impaired G-protein-mediated adenylyl cyclase stimulation. The recovery from desipramine desensitization was age dependent. beta-Adrenoceptor density recovered more slowly in the cerebral cortex and the submandibular gland in 24-month-old rats than in 6-month-old rats. In contrast, in 12-month-old rats, there was a receptor up-regulation and adenylyl cyclase supersensitivity. These data indicate that the capacity for receptor modulation is age dependent and suggest that desipramine treatment may down-regulate stimulatory G protein.

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