Abstract
Rat brain homogenates prepared in 0.3 M sucrose solution were separated by high speed centrifugation into an R fraction containing the particulate material and an S fraction containing the soluble cytoplasm. The ratio (R/S) of concentrations of norepinephrine in the 2 fractions, referable to the stored reserves and free form, was 1.158.
The increased brain norepinephrine concentrations following oral administration of the monoamine oxidase inhibitors, trans-2-phenylcyclo-propylamine (SKF 385) and iproniazid, were distributed proportionately between the R and S fractions, so that the R/S ratio was essentially unchanged.
Intraperitoneal injection of reserpine released norepinephrine from the stored reserves into the soluble cytoplasmic fraction within 15 minutes. Subsequently, the concentration of the amine in the S fraction was reduced to a negligible level. Oral administration of SKF 385 did not reverse the depletion action of reserpine.
Intraperitoneal injection of reserpine to rats pretreated with SKF 385 erased the accumulated excess of norepinephrine but did not reduce the concentration below normal levels. The R/S ratio was unchanged.
The implication of these results to the mode of action of the drugs is discussed.
Footnotes
- Received November 18, 1959.
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