Long-term dexamethasone treatment diminishes store-operated Ca2+ entry in salivary acinar cells

Abstract

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na+-K+-2Cl− cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca2+ in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca2+ and Ca2+ ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca2+-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca2+ entry, resulting in hyposalivation in mouse submandibular glands.

Analysis of the Efficacy of Two Treatment Protocols for Patients with Symptomatic Oral Lichen Planus: A Randomized Clinical Trial

“…Prolonged contact with the oral mucosa should be avoided, as it can damage mucosal barriers and induce local immunosuppression, predisposing to oropharyngeal candidiasis, one of the most common side effects of topical corticosteroid therapy [ 42 ]. The literature reports several cases of non-response to treatment, associated with a clinical and symptomatological worsening of the disease [ 35 ].…”

“…Hyaluronic acid has aroused considerable interest, as several studies have indicated that it has significant benefits in the management of OLP [ 32 , 33 , 34 ]. The antibacterial activity of calcium hydroxide and umbelliferone can be used in the treatment of Lichen as alterations in the oral microbiota are among its potential etiological factors [ 35 ].…”

Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts

“…Furthermore, a small amount of IL-1β has been shown to be beneficial for periodontal remodeling, including wound healing, whereas IL-1β overproduction has been demonstrated to play a role in periodontal disease etiologies [ 8 ]. To analyze tooth movement in vitro, established models exist where PDL cells are treated with comparable pressure applications or physiological concentrations of IL-1β [ 1 , 9 , 10 , 11 , 12 ].…”

Clinical appearance of oral lesions in bronchial asthma patients using inhalation drug

“…Corticosteroid affects the expression or function of channels and transporters such as Ca 2+ signaling that is important in the saliva secretion mechanism resulting in decreases of saliva secretion. 18 Corticosteroid also reduces the expression of the enzyme phospholipase A 2 , lead to decreases of arachidonic acid and the transcription of inflammation mediators that is important in the mucosal defense system, this makes oral mucosa more susceptible to infection. 19 Beta 2 receptors also present at salivary glands cells, considering that beta 2 agonist acts by bonded to the receptors and this binds increases cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA) that can act by interfering Ca 2+ that is important in saliva secretion.…”