CA2-ADRENERGIC AGONISTS IS UP-REGULATED IN LACRIMAL AND SUBMANDIBULARGLANDS IN A MURINE MODEL OF SJOGRENS-SYNDROME( SIGNALING BY CHOLINERGIC AND ALPHA(1))

Innervation of the lacrimal gland of MRL/Mp-Fas-lpr/lpr (MRL/lpr), a m urine model for Sjogren's syndrome, is unaltered with the onset or pro gression of the lymphocytic infiltration. To determine whether lacrima l and submandibular gland cells are able to respond to external stimul i, 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 fluores cent dye fura-2 to monitor changes in the intracellular Ca2+ concentra tion ([Ca2+](i)) in response to cholinergic and alpha(1)-adrenergic st imulation, two major stimuli of lacrimal gland protein secretion. Chol inergic-induced [Ca2+](i) increase was up-regulated 3- and 4-fold in l acrimal gland acini isolated from 8- and 12-week-old MRL/lpr mice, res pectively, compared to 4-week-oId animals, but was not up-regulated in age-matched MRL/+ control mice. Similarly, alpha(1)-adrenergic-induce d [Ca2+](i) increase was up-regulated 7- and 12-fold in acini isolated from 8- and 12-week-old MRL/lpr mice, respectively, compared to 4-wee k-old animals, but was not up-regulated in MRL/+ mice. Cholinergic-ind uced [Ca2+](i) increase in submandibular gland acini of MRL/lpr and MR L/+ mice was the same at all ages. In contrast, alpha(1)-adrenergic-in duced [Ca2+](i) increase was up-regulated 3-fold in acini from 12-week -old MRL/lpr mice, compared to 4-week-old mice, but was not up-regulat ed in age-matched MRL/+ mice. We conclude that the Ca2+ signaling port ion of cholinergic and alpha(1)-adrenergic pathway in the lacrimal gla nd and the Ca2+ signaling portion of alpha(1)-adrenergic pathway in th e submandibular gland is up-regulated with the onset and progression o f the lymphocytic infiltration in the MRL/lpr murine model of Sjogren' s syndrome. (C) 1998 Academic Press.