A new type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative
Beaujouan, J.C.; Torrens, Y.; Viger, A.; Glowinski, J.
Molecular Pharmacology 26(2): 248-254
1984
ISSN/ISBN: 0026-895X PMID: 6207421 Document Number: 231818
A new ligand for investigating tachykinin-binding site subtypes was synthesized by coupling the 125I-Bolton and Hunter reagent to eledoisin (125I-BHE). Using a synaptosomal preparation (P2 fraction) of rat cerebral cortex, 125I-BHE was shown to bind with apparent high affinity (apparent Kd = 15.3 nM). When concentrations of up to 30 nM 125I-BHE were used, 125I-BHE binding was specific, saturable, reversible, and temperature-dependent. In contrast to [3H]dopamine, 125I-BHE was not taken up within synaptosomes by an ouabain-sensitive process. Eledoisin, kassinin, and substance P were examined for their ability to inhibit specific 125I-BHE binding to cortical synaptosomes. Eledoisin and kassinin were considerably more potent than substance P, in contrast to the order of potency observed for specific 125I-Bolton-Hunter substance P (125I-BHSP) binding. Specific 125I-BHE binding was highest in the cerebral cortex and hypothalamus; intermediate in the hippocampus, striatum, and thalamus; low in the mesencephalon, septum, and substantia nigra; and absent in the cerebellum. Comparison of these data with those previously obtained for 125I-BHSP binding to synaptosomes indicated that 125I-BHE-labeled binding sites differ markedly from those of 125I-BHSP-labeled binding sites. Therefore, tachykinin receptors other than substance P receptors seem to be present in the central nervous system.