Inhibitory effects of ruthenium red on inositol 1,4, 5-trisphosphate-induced responses in rat megakaryocytes.
The effects of ruthenium red (RR) on inositol 1,4,5-trisphosphate (InsP(3))-induced responses were studied in rat bone marrow megakaryocytes with the patch-clamp whole-cell recording technique in combination with fura-2 microfluorometry. Internal application of InsP(3) (100 microM) increased intracellular Ca(2+) concentration ([Ca(2+)](i)) and activated the Ca(2+)-dependent K(+) current. Administering InsP(3) together with RR (100-500 microM) inhibited InsP(3)-induced responses (both Ca(2+) and current responses) in a dose-dependent fashion. Pretreatment of megakaryocytes with extracellular RR (50 microM) also inhibited InsP(3)-induced responses. Intracellular and extracellular application of RR reduced ADP-induced increases in [Ca(2+)](i). In contrast, in isolated single pancreatic acinar cells, RR had no effect on InsP(3)-induced responses. Taken together, these results suggest that the site of the inhibitory action of RR is at the InsP(3) receptor, or its closely associated proteins. In addition, we have shown that RR is a useful pharmacological tool with which to examine the InsP(3)-mediated responses of megakaryocytes.
Ikeda
M
M
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, 1-1 Gakuenki-banadai-nishi 889-2192, Miyazaki, Japan. a0d302u@cc.miyazaki-u.ac.jp
Maruyama
Y
Y
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D005456:Fluorescent Dyes / Q000378:metabolism; D016257:Fura-2 / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology*
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D012430:Ruthenium Red; D000244:Adenosine Diphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2