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Molecular Pharmacology, Vol 11, 369-378, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Barbiturate Inhibition of Calcium Uptake by Depolarized Nerve Terminals in Vitro

M. P. BLAUSTEIN 1 and A. CHRISTIE ECTOR 1

1 Department of Physiology and Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110

The effect of barbiturates on 45Ca uptake by pinched-off presynaptic terminals (synaptosomes) from rat brain has been examined. Calcium uptake is stimulated by depolarizing agents (potassium, veratridine, or gramicidin D), and this extra uptake is inhibited by sodium pentobarbital; 0.4-0.5 mM pentobarbital reduces the extra uptake by 50%. Sodium thiopental is also effective and, at a concentration of 0.2 mM, reduces the potassium-stimulated calcium uptake by about 50%. In one experiment, 0.9 mM sodium phenobarbital exhibited little inhibitory effect on calcium uptake. Two other central depressants, ethanol (100 mM) and chloroform (3-12 mM), had no significant effect on the potassium-stimulated calcium uptake. The inhibitory action of pentobarbital did not appear to involve competition between the barbiturate and external calcium. Also, the calcium entry which was promoted by raising internal and lowering external sodium was only slightly reduced by pentobarbital; this indicates that the inhibitory action of pentobarbital is limited primarily to the calcium entry triggered by depolarizing agents. The data are compatible with the idea that pentobarbital and thiopental may interfere with transmitter release and synaptic transmission by reducing the depolarization-triggered calcium entry in presynaptic terminals.

Note:
ACKNOWLEDGMENTS We thank Dr. J. A. Ferrendelli for the sample of (+)-DMBB, and Dr. R. Wette for assistance with the statistical analysis of the data.

Submitted on December 23, 1974




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R. Nicoll
Pentobarbital: differential postsynaptic actions on sympathetic ganglion cells
Science, January 27, 1978; 199(4327): 451 - 452.
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