Factors Contributing to the Modulation of Norepinephrine Uptake by Synaptosomes from Mouse Brain Cortex

The mode of inheritance of the synaptosomal mechanism for uptake of norepinephrine (NE) was studied in two inbred strains of mice, BALB/cBY and C57BL/6BY, along with the reciprocal F1 hybrids and 7 recombinant inbred strains, CXBD, CXBE, CXBG,CXBH,CXBI,CXBJ and CXBK. All these strains were also tested in the open field as a measure of response to mild stress, since stress had been shown to affect the kinetic constants of synaptosomal uptake. The two parental strains show a significant difference in Km for NE uptake similar to that previously reported between BALB/cJ and C57BL/10J, and no significant difference in V max. The F1 hybrids resemble C57BL/6BY, and the recombinant inbred strains show no significant differences from either parent with only minor exceptions. This makes further genetic analysis impossible with the data available at this time. A high positive correlation exists between Km and Vmax (r=0.89). The affinity for NE uptake and the number of uptake sites available seem to be modulated in a coordinated fashion. When the data on Km for all strains tested are pooled, a bimodal distribution is apparent. There are two populations with means of 2.25 and 4.03 x 10-7 M, respectively. Analysis of open field ambulation enables the strains to be divided into a high (C57BL/6BY, BXCF1, CXBF1, CXBD, CXBE, and CXBK) and a low group (BALB/cBY, CXBG, CXGH, CXGI and CXBJ). There is a significant negative interstrain correlation (r=0.87) between open field ambulation and Km for NE uptake. If we take open field ambulation as an index of reactivity to stress (high ambulation-low reactivity and vice versa), then we can regroup the data on NE uptake into two categories: 78% of the mice from the highly reactive strains presents high Km for NE uptake, while only 35% of the non-reactive mice show high Km. The bimodal distribution is apparent in both cases and the means of both high Km groups are identical; the same is true of the means for both low Km groups of strains of mice. It appears that Km for NE uptake does not vary along a continuum but it presents two discrete values. This would be suggestive of the existence of two distinct conformational states for the presumably proteinic uptake site. Stress presumably causes a switch from the high affinity conformation to the low affinity conformation. Thus a higher percentage of individuals from strains highly reactive to stress shows low affinity for NE uptake.