Ca2+Signaling by Cholinergic and α1-Adrenergic Agonists Is Up-Regulated in Lacrimal and Submandibular Glands in a Murine Model of Sjögren's Syndrome

Abstract

Innervation of the lacrimal gland of MRL/Mp-Fas-lpr/lpr(MRL/lpr), a murine model for Sjögren's syndrome, is unaltered with the onset or progression of the lymphocytic infiltration. To determine whether lacrimal and submandibular gland cells are able to respond to external stimuli, acini were prepared from MRL/lpr (diseased) and MRL/Mp-+/+ (MRL/+, control) mice at 4, 8, and 12 weeks of age and loaded with the fluorescent dye fura-2 to monitor changes in the intracellular Ca²⁺concentration ([Ca²⁺]_i) in response to cholinergic and α₁-adrenergic stimulation, two major stimuli of lacrimal gland protein secretion. Cholinergic-induced [Ca²⁺]_iincrease was up-regulated 3- and 4-fold in lacrimal gland acini isolated from 8- and 12-week-old MRL/lpr mice, respectively, compared to 4-week-old animals, but was not up-regulated in age-matched MRL/+ control mice. Similarly, α₁-adrenergic-induced [Ca²⁺]_iincrease was up-regulated 7- and 12-fold in acini isolated from 8- and 12-week-old MRL/lpr mice, respectively, compared to 4-week-old animals, but was not up-regulated in MRL/+ mice. Cholinergic-induced [Ca²⁺]_iincrease in submandibular gland acini of MRL/lpr and MRL/+ mice was the same at all ages. In contrast, α₁-adrenergic-induced [Ca²⁺]_iincrease was up-regulated 3-fold in acini from 12-week-old MRL/lpr mice, compared to 4-week-old mice, but was not up-regulated in age-matched MRL/+ mice. We conclude that the Ca²⁺signaling portion of cholinergic and α₁-adrenergic pathway in the lacrimal gland and the Ca²⁺signaling portion of α₁-adrenergic pathway in the submandibular gland is up-regulated with the onset and progression of the lymphocytic infiltration in the MRL/lpr murine model of Sjögren's syndrome.