Inhibitors of the intracellular Ca2+ release mechanism prevent muscarinic-induced Ca2+ influx in rat sublingual mucous acini.
The effects of inhibitors of the intracellular Ca2+ 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 [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.
Department of Dental Research, University of Rochester, NY 14642.
G H
GH
Zhang
J E
JE
Melvin
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology*; D016257:Fura-2 / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013361:Sublingual Gland / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007295:Inositol Phosphates; D013729:Terpenes; C081655:inositol-1,3,4,5-tetrakisphosphate; D008345:Manganese; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D003620:Dantrolene; D002118:Calcium; D016257:Fura-2