Expression of the noradrenaline transporter in the peripheral nervous system

Abstract

The noradrenaline transporter (NAT) transfers noradrenaline released into the synaptic cleft back into the presynaptic terminal, thus terminating neurotransmission. Although the distribution of NAT within the central nervous system has been well-characterized, less is known about its distribution elsewhere in the peripheral nervous system and in organs such as the skin. To address this in the present study, NAT expression was investigated using immunohistochemistry in the hind paw skin and more proximally in the sciatic nerve, dorsal root ganglia and spinal cord of five male Wistar rats. It was hypothesised that NAT would be expressed exclusively on nerve fibres labelled by dopamine beta hydroxylase (DβH), an enzyme involved in the conversion of dopamine to noradrenaline. NAT co-localised with DβH in neurons in the spinal cord, dorsal root ganglia and sciatic nerve. Unexpectedly, however, NAT-like immunoreactivity was not observed in DβH immuno-reactive fibres that innervated dermal blood vessels, suggesting that a mechanism other than presynaptic re-uptake of noradrenaline through NAT regulates transmission at neurovascular junctions in the skin. Furthermore, a novel association between NAT-like immunoreactivity and the myelin marker myelin basic protein (MBP) was identified in peripheral nerves. Specifically, NAT and MBP appeared to congregate around primary afferent nerve fibres labelled by neurofilament 200, a marker of neurons with medium- and large-diameter axons. NAT-like immunoreactivity was also detected in cultured Schwann cells immunohistochemically and at the mRNA level. Together, these findings imply a hitherto unrecognised role of Schwann cells in clearance of noradrenaline in the peripheral nervous system.