Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps.
Xerostomia and pathological thirst are troublesome complications of diabetes mellitus associated with impaired functioning of salivary glands; however, their cellular mechanisms are not yet determined. Isolated acinar cells were loaded with Ca2+ indicators fura-2/AM for measuring cytosolic Ca2+ concentration ([Ca2+]i) or mag-fura-2/AM-inside the endoplasmic reticulum (ER). We found a dramatic decrease in pilocarpine-stimulated saliva flow, protein content and amylase activity in rats after 6 weeks of diabetes vs. healthy animals. This was accompanied with rise in resting [Ca2+]i and increased potency of acetylcholine (ACh) and carbachol (CCh) but not norepinephrine (NE) to induce [Ca2+]i transients in acinar cells from diabetic animals. However, [Ca2+]i transients mediated by Ca2+ release from ER stores (induced by application of either ACh, CCh, NE, or ionomycin in Ca2+-free extracellular medium) were decreased under diabetes. Application of inositol-1,4,5-trisphosphate led to smaller Ca2+ release from ER under the diabetes. Both plasmalemma and ER Ca2+-ATPases activity was reduced and the latter showed the increased affinity to ATP under the diabetes. We conclude that the diabetes caused impairment of salivary cells functions that, on the cellular level, associates with Ca2+ overload, increased Ca2+-mobilizing ability of muscarinic but not adrenergic receptors, decreased Ca2+-ATPases activity and ER Ca2+ content.
Fedirko
N V
NV
Biological Department, I.Franko Lviv National University, 4 Grushevsky St., Lviv 79005, Ukraine. fedirn01@med.nyu.edu
Kruglikov
I A
IA
Kopach
O V
OV
Vats
J A
JA
Kostyuk
P G
PG
Voitenko
N V
NV
D000109:Acetylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006706:Homeostasis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015759:Ionomycin / Q000378:metabolism; D007476:Ionophores / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism*; D013894:Thirst; D014987:Xerostomia / Q000209:etiology / Q000378:metabolism
D005456:Fluorescent Dyes; D007476:Ionophores; C049925:fura-2-am; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine