Characteristics of norepinephrine uptake in developing peripheral nerve terminals.

In the chick the various characteristics of [3H]norepinephrine (NE) uptake do not appear simultaneously during the development of the iris. Na+-dependence and ouabain sensitivity are both first seen at a significant level at 10 days of incubation (d.i.). Na+-dependence achieves its peak value at 14 d.i. and is unchanged at 3 months after hatching (a.h.). Ouabain sensitivity increases after its initial appearance to 14 days a.h. and then slowly declines. Temperature sensitivity develops only at hatching and is modified subsequently. Both desmethylimipramine (DMI) and cocaine inhibition develop at 10 d.i. and follow the same developmental pattern; however, DMI appears to be a more effective inhibitor than cocaine. Metanephrine, an inhibtor of extraneuronal uptake, first inhibits NE uptake to a significant degree at hatching. These changes may be related to changes in membrane structure and metabolic function in the developing neuronal membrane. No evidence of [3H]NE uptake is seen at 7 d.i. After this age the Km values tend to fall into two groups, the first 1.3--1.9 X 10(-5) M, up to one month a.h., the second, 3.5--5.0 X 10(-6) M, after one month a.h. There is a large increase in Vmax from 10 to 14 d.i., a period of rapid growth of sympathetic innervation of the iris. Our study suggests that Na+-dependent uptake is a more reliable and constant index of innervation in development than temperature-dependent uptake. It also indicates that in longitudinal developmental studies it is necessary to determine the characteristrics of the transport process of each stage, as characteristics such as N1+-, drug- and temperature-sensitivity may all have unique developmental profiles.