Desipramine desensitizes beta-adrenergic signal transduction in rat salivary glands.
The consequences of the tricyclic antidepressant drugs include sedation, orthostatic hypotension and salivary dysfunction. It was reported that administration of desipramine resulted in a decrease in the concentration of secreted salivary protein. Tricyclic antidepressants may indirectly alter salivary function as a result of their action on the central nervous system to decrease adrenergic neural transmission or, alternately, may act directly on salivary glands to modulate beta-adrenergic signal transduction. To investigate the latter possibility, the effects of administration of desipramine (DMI) for 28 days was assessed on beta-adrenergic and post-receptor signal transduction in the parotid and submandibular glands of the rat and the reversibility of this treatment following a washout period of 15 days. Both glands demonstrated desensitization of the isoproterenol-stimulated activity, and in the parotid gland treatment with DMI decreased the post-receptor signal transduction as well. The washout period of 15 days completely reversed the desensitization in the parotid gland and partially reversed the effects in the submandibular gland. These data suggest that desipramine-induced attenuation of beta-adrenergic signal transduction is not limited to the brain and that these direct effects on salivary glands may explain the salivary dysfunction observed after administration of desipramine.
Scarpace
P J
PJ
Department of Veterans Affairs Medical Center, Gainesville, FL 32608-1197.
Koller
M M
MM
Rajakumar
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012469:Salivary Glands / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000262:Adenylyl Cyclases; D003891:Desipramine