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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Axonal transport of beta-adrenergic receptors. Antero- and retrogradely transported receptors differ in agonist affinity and nucleotide sensitivity.

Beta-receptors were measured in longitudinal sections of ligated rat sciatic nerve by autoradiographic localization of 125I-labeled cyanopindolol binding sites. Receptors accumulated at the ligature, both proximally and distally, in a time-dependent fashion. Receptor transport also occurred in an isolated segment of nerve (i.e., a doubly ligated nerve), suggesting that the movement is by fast transport. Pharmacological analysis of the accumulating binding sites indicates that they are beta 2-adrenergic receptors. In competition studies, agonists were 10-30 times more potent on receptors accumulating proximal to the ligature than on distally accumulating receptors, whereas antagonists were equipotent on both. Guanyl-5'-yl-imidodiphosphate (GppNHp) decreased the potency of agonists at proximal receptors in a dose-dependent fashion. Distal receptors were much less sensitive to GppNHp. Other nucleotides displayed varying abilities to mimic the effect of GppNHp, suggesting the involvement of a guanine nucleotide-binding protein in regulating agonist affinity. Thus, presynaptic beta 2-adrenergic receptors were identified in rat sciatic nerve. A small fraction of them apparently moves by fast transport. The anterogradely transported receptors have binding properties which differ from the retrogradely moving receptor and appear to be in functional association with a nucleotide regulatory protein.[1]


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