Locomotor activity and blood pressure in conscious mice with targeted deletion of the equilibrative nucleoside transporter 1

Abstract

Extracellular adenosine (ado) is regulated by transmembrane transport through both equilibrative and concentrative nucleoside transporters (ENTs and CNTs). Previous studies have reported profound effects of extracellular ado on sleep, anxiety, and locomotor activity. The present experiments were performed in ENT1‐deficient mice to assess the long term effect of impaired ado exchange on arterial blood pressure (MAP) and locomotor activity. Average daily running wheel activity (RWA, revolutions/min) under LD (12h light:12h dark) and DD (24 h dark) was markedly reduced in ENT1 −/− (LD, 3.1 ± 0.1; DD, 2.1 ± 0.1; n=4) vs. WT mice (LD, 9.4 ± 0.7; DD, 11.3 ± 0.3; n=4; p < 0.001). RWA showed comparable circadian periodicity between genotypes, but the periodic strength was greater in WT than ENT1−/−. Spontaneous activity measured with radiotransmitters was also 40% lower in ENT1−/− than WT mice. Telemetric measurements of MAP showed no significant differences between genotypes although pulse pressure was lower in −/− than +/+ mice. Heart rates were lower in ENT1−/− than WT by about 40 bpm during both light and dark periods. Plasma renin concentration (ng Ang I/ml hr) tended to be lower in ENT1 −/− mice without reaching significance. Absence of ENT1 is associated with reduced locomotor activity, perhaps reflecting suppression of neuronal activities by impaired ado transporting capacity.