title: Factors contributing to the modulation of norepinephrine uptake by synaptosomes from mouse brain cortex.
abstract: 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.
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D014644:Genetic Variation; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D009638:Norepinephrine