Tenidap, an anti-inflammatory agent, discharges intracellular Ca++ store and inhibits Ca++ influx in cultured human gingival fibroblasts.
The effect of tenidap, (+/-)-5-chloro-2,3-dihydro-3-(hydroxy-2- thienylmethylene)-2-oxo-1H-indole-1-carboxamide, a new anti-inflammatory agent, was investigated on intracellular free Ca++ concentration ([Ca++]i) responses evoked by bradykinin and thapsigargin in gingival fibroblasts. Tenidap itself stimulated [Ca++]i response in a dose-dependent manner in the absence of extracellular Ca++. The pretreatment with tenidap inhibited [Ca++]i responses evoked by 5 nM bradykinin and 1 microM thapsigargin in a dose-dependent manner. This indicates that tenidap discharges intracellular Ca++ store, resulting in a depletion of intracellular Ca++ store. Tenidap partially depressed Ca++ influx across plasma membrane by 1 to 2 min pretreatment and almost completely by more than 5 min pretreatment. Thus, tenidap appears to be a valuable agent that functions on inhibition of Ca++ influx in nonexcitable cells, which is rare at the present time.
Fujii
A
A
Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Matsumoto
H
H
Hashimoto
T
T
Akimoto
Y
Y
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D000078183:Oxindoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; C062866:tenidap; D002118:Calcium