RT Journal Article
SR Electronic
T1 α-Amanitin Inhibition of Mouse Brain Form II Ribonucleic Acid Polymerase and Passive Avoidance Retention
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 146
OP 154
VO 10
IS 1
A1 PAUL D. THUT
A1 THOMAS J. LINDELL
YR 1974
UL http://molpharm.aspetjournals.org/content/10/1/146.abstract
AB Injection of α-amanitin into a cerebral ventricle reduced the ability of male mice to retain a passive avoidance response without affecting spontaneous locomotor activity or performance of a previously learned task. α-Amanitin inhibited the brain form II DNA-dependent RNA polymerase in a dose-dependent manner up to 10 µg, at which dose a maximum of 98% inhibition was observed as determined by assay of brain nuclei at the time of training. The effect observed on passive avoidance retention is only seen at maximal (98%) inhibition. Furthermore, the inhibition of brain form II polymerase is transient, indicating that α-amanitin is effective in vivo only when virtually 100% inhibition of this enzyme is attained. The liver form II polymerase was also inhibited after cerebroventricular injection, indicating that a significant amount of the α-amanitin reached peripheral circulation. A 50% inhibition of liver form II polymerase was measured within 15 min. However, intraperitoneal injection of 10 µg of α-amanitin did not produce significant inhibition of brain form II polymerase, and retention of a passive avoidance response was not affected. ACKNOWLEDGMENTS We thank Professor T. Wieland for a generous gift of α-amanitin. The expert technical assistance of Sandra Burt , Royal Ellinger, Tony O'Malley, James Warren, Colleen Bentley, and Janet Neuberg is gratefully acknowledged. We thank Dr. Rubin Bressler for continued interest and support.