Histamine H and H receptor activation increases the expression of Glucose Transporter 1 (GLUT-1) in rat cerebro-cortical astrocytes in primary culture.

Astrocytes take up glucose via the 45 kDa isoform of the Glucose Transporter 1 (GLUT-1), and in this work we have investigated whether histamine regulates GLUT-1 expression in rat cerebro-cortical astrocytes in primary culture. Cultured astrocytes expressed histamine H and H receptors (HRs and HRs) as evaluated by radioligand binding. Receptor functionality was confirmed by the increase in the intracellular concentration of Ca (HR) and the inhibition of forskolin-induced cAMP accumulation (HR). Quantitative RT-PCR showed that histamine and selective HR and HR agonists (1 h incubation) significantly increased GLUT-1 mRNA to 153 ± 7, 163 ± 2 and 168 ± 13% of control values, respectively. In immunoblot assays, incubation (3 h) with histamine or HR and HR agonists increased GLUT-1 protein levels to 224 ± 12, 305 ± 11 and 193 ± 13% of control values, respectively, an action confirmed by inmunocytochemistry. The effects of HR and HR agonists were blocked by the selective antagonists mepyramine (HR) and clobenpropit (HR). The pharmacological inhibition of protein kinase C (PKC) prevented the increase in GLUT-1 protein induced by either HR or HR activation. Furthermore, histamine increased ERK-1/2 phosphorylation, and the effect of HR and HR activation on GLUT-1 protein levels was reduced or prevented, respectively, by MEK-1/2 inhibition. These results indicate that by activating HRs and HRs histamine regulates the expression of GLUT-1 by astrocytes. The effect appears to involve the phospholipase C (PLC) → diacylglycerol (DAG)/Ca→ PKC and PLC → DAG/Ca → PKC → MAPK pathways.