PMID- 11082216
OWN - NLM
STAT- MEDLINE
DCOM- 20001222
LR  - 20221011
IS  - 0037-9727 (Print)
IS  - 0037-9727 (Linking)
VI  - 225
IP  - 3
DP  - 2000 Dec
TI  - Characterization of the calcium signaling system in the submandibular cell line 
      SMG-C6.
PG  - 211-20
AB  - Establishment of salivary cell lines retaining normal morphological and 
      physiological characteristics is important in the investigation of salivary cell 
      function. A submandibular gland cell line, SMG-C6, has recently been established. 
      In the present study, we characterized the phosphoinositide (PI)-Ca2+ signaling 
      system in this cell line. Inositol 1,4,5-trisphosphate(1,4,5-IP3) formation, as 
      well as Ca2+ storage, release, and influx in response to muscarinic, 
      alpha1-adrenergic, P2Y-nucleotide, and cytokine receptor agonists were 
      determined. Ca2+ release from intracellular stores was strongly stimulated by 
      acetylcholine (ACh) and ATP, but not by norepinephrine (NA), epidermal growth 
      factor (EGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha). 
      Consistently, 1, 4,5-IP3 formation was dramatically stimulated by ACh and ATP. 
      ACh-stimulated cytosolic free Ca2+ concentration [Ca2+]i increase was inhibited 
      by ryanodine, suggesting that the Ca2+-induced Ca2+ release mechanism is involved 
      in the ACh-elicited Ca2+ release process. Furthermore, ACh and ATP partially 
      discharged the IP3-sensitive Ca2+ store, and a subsequent exposure to 
      thapsigargin (TG) induced further [Ca2+]i increase. However, exposure to TG 
      depleted the store and a subsequent stimulation with ACh or ATP did not induce 
      further [Ca2+]i increase, suggesting that ACh and ATP discharge the same storage 
      site sensitive to TG. As in freshly isolated submandibular acinar cells, exposure 
      to ionomycin and monensin following ACh or TG induced further [Ca2+]i increase, 
      suggesting that IP3-insensitive stores exist in SMG-C6 cells. Ca2+ influx was 
      activated by ACh, ATP, or TG, and was significantly inhibited by La3+, suggesting 
      the involvement of store-operated Ca2+ entry (SOCE) pathway. These results 
      indicate that in SMG-C6 cells: (i) Ca2+ release is triggered by muscarinic and 
      P2Y-nucleotide receptor agonists through formation of IP3; (ii) both the 
      IP3-sensitive and -insensitive Ca2+ stores are present; and (iii) Ca2+ influx is 
      mediated by the store-operated Ca2+ entry pathway. We conclude that Ca2+ 
      regulation in SMG-C6 cells is similar to that in freshly isolated SMG acinar 
      cells; therefore, this cell line represents an excellent SMG cell model in terms 
      of intracellular Ca2+ signaling.
FAU - Liu, X B
AU  - Liu XB
AD  - Secretory Cell Physiology Laboratory, Department of Pediatrics, University of 
      Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
FAU - Sun, X
AU  - Sun X
FAU - Mork, A C
AU  - Mork AC
FAU - Dodds, M W
AU  - Dodds MW
FAU - Martinez, J R
AU  - Martinez JR
FAU - Zhang, G H
AU  - Zhang GH
LA  - eng
GR  - DE09270/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Soc Exp Biol Med
JT  - Proceedings of the Society for Experimental Biology and Medicine. Society for 
      Experimental Biology and Medicine (New York, N.Y.)
JID - 7505892
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, Purinergic P2)
RN  - 67526-95-8 (Thapsigargin)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - N9YNS0M02X (Acetylcholine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - *Calcium Signaling/drug effects
MH  - Cell Line
MH  - Inositol 1,4,5-Trisphosphate/biosynthesis
MH  - Models, Biological
MH  - Norepinephrine/pharmacology
MH  - Phosphatidylinositols/metabolism
MH  - Rats
MH  - Receptors, Muscarinic/drug effects/metabolism
MH  - Receptors, Purinergic P2/drug effects/metabolism
MH  - Submandibular Gland/cytology/drug effects/*metabolism
MH  - Thapsigargin/pharmacology
EDAT- 2000/11/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
AID - pse22527 [pii]
AID - 10.1177/153537020022500308 [doi]
PST - ppublish
SO  - Proc Soc Exp Biol Med. 2000 Dec;225(3):211-20. doi: 10.1177/153537020022500308.