Four NT receptors have been identified, two that are 7-transmembrane G protein-coupled receptors (NTR-1, NTR-2) and two primarily intracellular proteins related to yeast sorting receptors (NTR-3/sortilin, NTR-4/SorLA). NTR-1 displays the highest affinity (Kd, 0.1 nM) and seems to mediate NT effects on dopaminergic transmission, hot-plate latency, temperature regulation, and smooth muscle contractility. First described as a lower affinity receptor (Kd, 3 nM) with a differing specificity, NTR-2 has been implicated in the analgesic effects of NT. Although the role of NTR-3 is less clear, one possibility is that through binding and internalizing NT this receptor serves to regulate turnover of the peptide. Evidence supports the involvement of NTR-3 in the growth-promoting effects of NT and in NT-induced migration of brain microglial cells.