title: A new type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative.
abstract: 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.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D004600:Eledoisin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000302:isolation & purification / Q000378:metabolism*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000494:pharmacology; D013388:Succinimides / Q000138:chemical synthesis / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D015320:Tachykinins
chemical_list: C043034:Bolton Hunter-eledoisin ligand; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010455:Peptides; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D013388:Succinimides; D015320:Tachykinins; D013373:Substance P; D004600:Eledoisin