Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling

The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function ( muscarinic agonist-stimulated saliva flow, intracellular calcium mobilizati on, Na+/K+/2Cl(-) cotransport activity) in rat submandibular glands 12 mont hs postirradiation (single dose, 10 Gy), The morphological status of glands from control and irradiated rats was also determined, Pilocarpine-stimulat ed salivary flow was decreased by 67% at 12 months (but not at 3 months) af ter irradiation, This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrat ed that acinar cells were smaller and occupied relatively less volume and c onvoluted granular tubules were smaller but occupied the same relative volu me, while intercalated and striated ducts maintained their size but occupie d a greater relative volume in submandibular glands from irradiated compare d to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilizat ion of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+](i) imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation t reatment. The carbachol-stimulated, bumetanide-sensitive component of the N a+/K+/2Cl(-) cotransport activity was also similar in submandibular gland c ells from control and irradiated animals. These data demonstrate that a sin gle dose of gamma radiation induces a progressive loss of submandibular gla nd tissue and function. This loss of salivary flow is not due to chronic in flammation or fibrosis of the gland or an alteration in the neurotransmitte r signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland. (C) 1999 by Radiation Research Society.