The effect of insulin on norepinephrine uptake by PC12 cells

doi:10.1016/0361-9230(93)90210-3

Brain Research Bulletin

Volume 32, Issue 4, 1993, Pages 425-431

https://doi.org/10.1016/0361-9230(93)90210-3 Get rights and content

Abstract

We have previously reported that insulin can enhance endogenous noradrenergic activity in vitro in the rat CNS. In the present study, we examined one potential mechanism underlying this effect: the ability of insulin to inhibit norepinephrine (NE) reuptake and secondarily increase its synaptic concentration. Acute (20 min) insulin treatment (0.1–10 nM) significantly inhibited specific ³H-norepinephrine uptake by rat hypothalamic slices. To ascertain whether this is a direct effect of insulin on cells that can synthesize and release norepinephrine, we studied NE uptake by the rat pheochromocytoma PC12 cell line. In PC12 cells, insulin (0.5–10 nM) inhibited NE uptake whereas the related peptide, insulin-like growth factor 1 (IGF-1), did not. Insulin did not compete with ³H-mazindol (a ligand for the NE reuptake transporter) binding to PC 12 cell membranes. Thus, this effect of insulin is not due to interaction with either IGF-1 receptors or the norepinephrine transporter, but may be due to insulin interaction with its own receptor. Chronic (96-h) insulin treatment of PC 12 cells also resulted in an inhibition of ³H-norepinephrine uptake, and membranes prepared from cells chronically treated with insulin bound less ³H-desipramine than control membranes. Thus, chronic insulin treatment may result in a decrease in the numbers of membrane-associated transporters. We conclude that insulin has a direct and physiological role in the modulation of synaptic norepinephrine levels by modulating reuptake by cells that synthesize and release norepinephrine.

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ArticleThe effect of insulin on norepinephrine uptake by PC12 cells

Abstract

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Biochim. Biophys. Acta

Anal. Biochem.

Exp. Eye Res.

Brain Res.

Neurosci. Lett.

Brain Res.

The transport of (+) amphetamine by the neuronal noradrenaline carrier

Naunyn Schmiedebergs Arch. Pharmacol.

Transport of noradrenaline across the cell membrane of isolated neuronal cells with special reference to PC12 cells

Binding of 3H-desipramine to the neuronal noradrenergic carrier of rat phaeochromocytoma cells (PC12 cells)

Naunyn Schmiedebergs Arch. Pharmacol.

Insulin and insulin-like growth factors stimulate deoxyribonucleic acid synthesis in PC 12 pheochromocytoma cells

Endocrinology

Article
The effect of insulin on norepinephrine uptake by PC12 cells

Binding of ³H-desipramine to the neuronal noradrenergic carrier of rat phaeochromocytoma cells (PC12 cells)