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Factors contributing to the modulation of norepinephrine uptake by synaptosomes from mouse brain cortex

Factors contributing to the modulation of norepinephrine uptake by synaptosomes from mouse brain cortex

Brain Research 121(1): 113-120

ISSN/ISBN: 0006-8993

PMID: 832147

DOI: 10.1016/0006-8993(77)90441-3

The mode of inheritance of the synaptosomal mechanism for uptake of norepinephrine (NE) was studied in 2 inbred stains of mice, BALB/cBy and C57BL/6By, along with the reciprocal F1 hybrids and 7 recombinant inbred stains, 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 2 parental strains showed a significant difference in Km for NE uptake similar to that previously reported between BALB/cJ and C57BL/10J, and no significant difference in Vmax. The F1 hybrids resembled C57BL/6By, and the recombinant inbred strains showed 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 existed between Km and Vmax (r = 0.89). The affinity for NE uptake and the number of uptake sites available seemed to be modulated in a coordinated fashion. When the data on Km for all strains tested are pooled, a bimodal distribution was apparent. There were 2 populations with means of 2.25 and 4.03 .times. 10-7 M, respectively. Analysis of open field ambulation enabled the strains to be divided into a high (C57BL/6By, BXCF1, CXBF1, CXBD, CXBE and CXBK) and a low group (BALB/cBy, CXBG, CXBH, CXBI and CXBJ). There was a significant negative interstrain correlation (r = 0.87) between open field ambulation and Km for NE uptake. If open field ambulation was taken as an index of reactivity to stress (high ambulation-low reactivity and vice versa), then the data could be regrouped on NE uptake into 2 categories: 78% of the mice from the highly reactive strains presented high Km for NE uptake, while only 35% of the non-reactive mice showed high Km. The bimodal distribution was apparent in both cases and the means of both high Km groups were 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 2 discrete values. This would be suggestive of the existence of 2 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.

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Accession: 005441149

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