Cyclosporin A: effects on the secretory process and noradrenergic activity in the submandibular gland of the rat.
OBJECTIVE
The aim of the present work was to study the effect of long-term cyclosporine (CSA) administration on norepinephrine (NE) metabolism and adrenergic-evoked secretion in the rat submandibular gland (SMG).


METHODS
Dose-response curves to adrenergic agonists (methoxamine, isoproterenol, NE) were performed in control and CSA (10 and 30 mg/kg every 2 days for 1 month)-treated rats after SMG duct cannulation. In SMG tissue neuronal NE uptake, release, synthesis and endogenous content were determined. In addition phosphoinositide intracellular signaling was also investigated.


RESULTS
CSA administration caused an increase in salivary secretion evoked by methoxamine (alpha-adrenergic agonist) and NE but failed to modify salivation evoked by beta-adrenergic stimulation (isoproterenol). Long-term CSA administration decreased NE release and synthesis whereas it enhanced the amine uptake and phosphoinositide hydrolysis in the SMG.


CONCLUSIONS
The administration of CSA for 30 days induced salivary gland sensitization likely mediated by diminished adrenergic input. Present results suggest that the decreased sympathetic activity evoked by long-term CSA administration in the rat SMG may lead to sensitization of the gland supported by increased phosphoinositide hydrolysis and enhanced adrenergic-evoked salivation.
Giglio
J M
JM
Cátedras de Patología y Clínica Bucodental y Fisiología, Facultad de Odontología Universidad de Buenos Aires, Argentina.
Vatta
M S
MS
Bianciotti
L G
LG
Lomniczi
A
A
Elverdin
J C
JC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006868:Hydrolysis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012472:Salivation / Q000187:drug effects* / Q000276:immunology; D013363:Submandibular Gland / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D007166:Immunosuppressive Agents; D010716:Phosphatidylinositols; D016572:Cyclosporine; D008729:Methoxamine; D009638:Norepinephrine