NOREPINEPHRINE CONCENTRATING MECHANISMS IN SYMPATHETIC NERVE TRUNKS

L. STJÄRNE ¹, R. H. ROTH ¹, F. E. BLOOM ¹, and N. J. GIARMAN ¹

¹ Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut

When bovine splenic nerve trunk is incubated with tritium-labeled norepinephrine, autoradiography at the electron microscopic level, as well as sucrose density gradient analysis of the subcellular distribution, demonstrates that the exogenous norepinephrine has penetrated throughout the preparation and has, to some extent, acquired the same intra-axonal distribution as endogenous norepinephrine. However, the concentrating mechanism of this "pure" nerve preparation does not appear very efficient; the tissue/medium ratio never greatly exceeds that observed in slices of spleen, in which nerve tissue represents a very small proportion of the total tissue mass. The uptake is increased 5-fold by raising the temperature from 0°C-37°C. It is depressed in the absence of sodium, not affected by reserpine, but partially blocked by desipramine. At 0°C the exogenous norepinephrine mixes only minimally with the endogenous particle-bound amine. At 37°C a 60% equilibration is approached in 30 minutes. This process is blocked by reserpine, but is only moderately counteracted by desipramine. Thus, with the present technique, the nerve trunk under study appears to possess a relatively inefficient norepinephrine-uptake mechanism. The exogenous amine which penetrates into the axon seems to be distributed between several different functional "poois." Both the autoradiographic data, the subcellular distribution studies and the observed effects of the drugs indicate that a certain proportion of the intra-axonal norepinephrine exists outside the particles in a state which renders it relatively well protected against attack by monoamine oxidase.