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Inhibitors of the intracellular Ca 2+ release mechanism prevent muscarinicinduced Ca 2+ influx in rat sublingual mucous acini
Author(s) -
Zhang Guo H.,
Melvin James E.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81026-v
Subject(s) - divalent , chemistry , intracellular , carbachol , thapsigargin , biophysics , inositol , stimulation , calcium , inositol trisphosphate , biochemistry , endocrinology , biology , receptor , organic chemistry
The effects of inhibitors of the intracellular Ca 2+ release mechanism on divalent cation fluxes were examined in acinar cells loaded with the Ca 2+ ‐sensitive, Mn 2+ ‐quenchable dye, fura‐2. TMB‐8 and dantrolene (DTL) dramatically inhibited the carbachol (CCh)‐stimulated increase in [Ca 2+ ] i and Mn 2+ influx. These agents do not directly inhibit divalent cation entry since addition of TMB‐8 or DTL after CCh stimulation did not block Mn 2+ influx. TMB‐8 did not influence the [Ca 2+ ] i increase or the Mn 2+ 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 Ca 2+ pool. TMB‐8 and DTL did not significantly influence the muscarinic‐stimulated production of inositol trisphosphate (IP 3 ) and inositol tetrakisphosphate (IP 4 ), although TMB‐8, but not DTL, did decrease the CCh‐stimulated 1,4,5‐IP 3 levels approximately 55%. The above results directly demonstrate that the filling state of the intracellular Ca 2+ store primarily regulates the Ca 2+ entry mechanism in sublingual mucous acinar cells.