Cyclosporin A: Effects on the Secretory Process and Noradrenergic Activity in the Submandibular Gland of the Rat

Abstract

Objectives: 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 (α-adrenergic agonist) and NE but failed to modify salivation evoked by β-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.

The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands

“…Due to the high lipophilicity of CsA, it is transferred from the blood to the saliva and can cause changes in the composition of the saliva. As a result, patients are at increased risk of oral infections, caries, and changes in taste, which may consequently lead to a decrease in quality of life [ 14 – 17 ].…”