Inhibition of transmitter release by TI233, a calmodulin antagonist, from clonal neural cells and a presumed site of action.
Effects of TI233, a calmodulin antagonist, on transmitter release were studied using a clonal pheochromocytoma cell line (PC12h). TI233, at a concentration of 30 microM, completely suppressed the release of preloaded [3H]NE and [3H]DA. The 50% suppression dose was around 3 microM. TI233 did not inhibit the [3H]NE release evoked by the calcium ionophore A23187. Electrophysiological examinations using a clonal neuroblastoma x glioma hybrid cell line (NG108-15) revealed that TI233 blocked the voltage-sensitive calcium channel of the membrane in the same concentration range. Thus it was suggested that TI233 inhibited transmitter release from neuronal cells by blocking the entry of calcium to the cytoplasm.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002999:Clone Cells; D004594:Electrophysiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D018377:Neurotransmitter Agents; C028964:TI 233; D001120:Arginine; D011188:Potassium