PT  - JOURNAL ARTICLE
AU  - R. D. KRELL
AU  - P. N. PATIL
TI  - STERIC ASPECTS OF ADRENERGIC DRUGS. XX. ACCUMULATION OF (-)- AND (+)-NOREPINEPHRINE-<sup>14</sup>C BY PERIPHERAL TISSUES OF THE RAT
DP  - 1972 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 273--283
VI  - 182
IP  - 2
4099  - http://jpet.aspetjournals.org/content/182/2/273.short
4100  - http://jpet.aspetjournals.org/content/182/2/273.full
SO  - J Pharmacol Exp Ther1972 Aug 01; 182
AB  - Ten minutes after i.v. infusion of either (-)-or (+)-norepinephrme-14C (NE-14C) into the rat, heart, spleen and vas deferens demonstrated an approximate 2-fold stemeoselective preference for (-)-NE-14C, suggesting a preferential accumulation of the (-)-isomer by storage vesicles. Four hours postinfusion, tissue levels of (-)-NE-14C were 2 to 3 times greater than (+)-NE-14C, indicating that the retention of the isomers in these tissues is also stereoselective for (-)-NE-14C. Slices of rat ventricle, spleen and vas deferens were incubated for times varying from 5 or 10 to 40 minutes with either (-)-or (+)-NE-14C ranging in concentration from 10 to 200 ng/ml. No stereoselective accumulation was apparent in any tissue, at any time or concentration. Kinetic constants determined in guanethidine-, iproniazid- and tropolone-pretreated slices demonstrated an approximate 2-fold stereoselective preference for (-)-NE-14C ; Vmax for the (+)-isomer was approximately twice that of the (-)-isomer. Guanethidine did not appear to impair the accumulation of either isomer by the "microsomal" fraction of rat vasa deferentia. The microsomal fraction represents the fraction containing amine storage vesicles. It is suggested that the 2-fold stereoselectivity apparent from kinetic data is due to storage vesicles; therefore, the neuronal membranes of rat heart, spleen and vas deferens do not appear to discriminate between the optical isomers of NE. However, among the isomers of cocaine, (-)-cocaine is 14 to 19 times more potent as an inhibitor of (-)-NE-14C uptake in ventricle and vas deferens slices than (+)-pseudococaine. © 1972 by The Williams & Wilkins Co.