Fluoride activates G protein-dependent and -independent pathways in dispersed intestinal smooth muscle cells.
The existence of G protein-dependent and -independent mechanisms activated by sodium fluoride was examined in muscle cells isolated separately from the circular and longitudinal layers of guinea pig intestine. The cells were transiently permeabilized by incubation with Trans. Port Reagent in the presence or absence of GDP beta S (100 microM) and then re-sealed. In the absence of GDP beta S, NaF (1 mM) induced contraction and caused an increase in [Ca2+]i, IP3 and diacylglycerol levels and in protein kinase C (PKC) activity in both cell types. In the presence of GDP beta S, the increases in IP3, DAG and PKC were abolished whereas contraction and the increase in [Ca2+]i were partly inhibited. Residual contraction and [Ca2+]i were abolished by the Ca2+ channel blocker, methoxyverapamil. We conclude that contraction and Ca2+ mobilization induced by NaF is mediated by G protein activation as well as by a G protein-independent mechanism involving activation of plasmalemmal Ca2+ channels.
Murthy
K S
KS
Department of Medicine, Medical College of Virginia, Richmond 23298.
Makhlouf
G M
GM
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D004075:Diglycerides; D007295:Inositol Phosphates; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D005459:Fluorides; D002118:Calcium