NaF-induced amylase release from rat parotid cells is mediated by PI breakdown leading to Ca2+ mobilization.
We have examined the effects of sodium fluoride (NaF) on amylase release, cellular adenosine 3',5'-cyclic monophosphate (cAMP) level, inositol phosphate formation, and cytosolic free Ca2+ concentration ([Ca2+]i) in dispersed rat parotid acini or cells. At concentrations greater than 1 mM, NaF significantly increased amylase release. The maximum response was observed at 10 mM NaF and was comparable to that of the muscarinic-cholinergic agonist carbachol. Removal of extracellular Ca2+ with EGTA markedly suppressed the NaF-induced secretory response. At concentrations up to 10 mM, NaF did not increase the cellular level of cAMP, indicating that the NaF-induced amylase release is not mediated by cAMP. NaF (1-20 mM) caused a slow increase in [Ca2+]i in a concentration-dependent manner, as monitored with the fluorescent Ca2+ indicator fura-2, and the increased [Ca2+]i did not decline for at least 10 min after addition of NaF. In the absence of extracellular Ca2+, NaF evoked only a small and transient increase in [Ca2+]i. The addition of 10 mM NaF produced a significant accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. These results suggest that the NaF-induced amylase release is mediated by a breakdown of phosphoinositides leading to Ca2+ mobilization. The effects of fluoride may be through the action of F- on the GTP-binding protein(s) coupled to phospholipase C.
Tojyo
Y
Y
Department of Dental Pharmacology, School of Dentistry, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Tanimura
A
A
Matsui
S
S
Matsumoto
Y
Y
Sugiya
H
H
Furuyama
S
S
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology
D007295:Inositol Phosphates; D002217:Carbachol; D012969:Sodium Fluoride; D013806:Theophylline; D000242:Cyclic AMP; D000681:Amylases; D002118:Calcium