Inhibitors of the intracellular Ca2+ release mechanism prevent muscarinicinduced Ca2+ influx in rat sublingual mucous acini

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Abstract
The effects of inhibitors of the intracellular Ca2+ release mechanism on divalent cation fluxes were examined in acinar cells loaded with the Ca2+‐sensitive, Mn2+‐quenchable dye, fura‐2. TMB‐8 and dantrolene (DTL) dramatically inhibited the carbachol (CCh)‐stimulated increase in [Ca2+]i and Mn2+ influx. These agents do not directly inhibit divalent cation entry since addition of TMB‐8 or DTL after CCh stimulation did not block Mn2+ influx. TMB‐8 did not influence the [Ca2+]i increase or the Mn2+ influx produced by thapsigargin. These results indicate that TMB‐8 and DTL do not interfere with divalent cation influx by inhibiting a step distal to depletion of the intracellular Ca2+ pool. TMB‐8 and DTL did not significantly influence the muscarinic‐stimulated production of inositol trisphosphate (IP3) and inositol tetrakisphosphate (IP4), although TMB‐8, but not DTL, did decrease the CCh‐stimulated 1,4,5‐IP3 levels approximately 55%. The above results directly demonstrate that the filling state of the intracellular Ca2+ store primarily regulates the Ca2+ entry mechanism in sublingual mucous acinar cells.