[Effect of TMB-8 on the increase of intracellular free Ca2+ induced by NE and BHQ in dissociated single rat brain cell].
The inhibitory effect and mechanism of 8-(N, N'-diethylamino) octyl 3, 4, 5-trimethoxybenzoate hydrochloride (TMB-8) on the elevation of single intracellular free Ca2+ concentration ([Ca2+]i) induced by High K+, Norepinephrine(NE) and 2, 5-Di(tert-butyl)-1, 4-benzohydroquinone (BHQ) in dissociated single rat brain cells were studied. The changes of [Ca2+]i were reflected by the fluorescent indicator, Fura-2/AM, employed. In the absence of extracellular Ca2+, Ca-free Hank's solution, preincubation with TMB-8 (10, 30 mumol.L-1) for 20 min significantly decreased the resting [Ca2+]i from 79 +/- 13 nmol.L-1 to 65 +/- 11 and 61 +/- 6 nmol.L-1, respectively. [Ca2+]i were markedly increased by NE and BHQ and reduced significantly to control level by TMB-8. On the other hand, when the cells were incubated in Hank's solution containing Ca2+ 1.3 mmol.L-1, TMB-8(30, 100 mumol.L-1) suppressed the increase of [Ca2+]i induced by NE (0.0001-0.1 mumol.L-1). TMB-8 showed no significant effect on [Ca2+]i elevation induced by KCl and BHQ in Hank's solution containing Ca2+ 1.3 mmol.L-1. These results indicate that TMB-8 reduced [Ca2+]i via increase of the sarcoplasmic reticulum (SR) sequestration, which blocked the release of intracellular store from the SR. However, the inhibitory effect of TMB-8 on Ca-influx from extracellular medium seems to be an indirect action from the saturation of SR with calcium.
Zhang
X Q
XQ
Department of Pharmacology, Nanjing Medical University, Nanjing 210029.
Wang
B
B
Zhang
M Y
MY
Xiao
J G
JG
D000818:Animals; D000831:Animals, Newborn; D001693:Biological Transport, Active; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006873:Hydroquinones / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D002118:Calcium; D009638:Norepinephrine