title: Pharmacological characterization of tachykinin septide-sensitive binding sites in the rat submaxillary gland.
abstract: Binding studies have shown that [125I]NKA is a selective ligand of tachykinin septide-sensitive binding sites from membranes of the rat submaxillary gland. Indeed, this ligand bound with high affinity to a single population of sites. In addition, competition studies indicated that natural tachykinins and tachykinin-related compounds had a similar affinity for these sites than for those labeled with [3H]ALIE-124, a selective ligand of septide-sensitive binding sites. Moreover, selective tachykinin NK2, or NK3 agonists or antagonists exhibited weak or no affinity for [125I]NKA binding sites. As indicated by Ki values of several compounds, the pharmacological characteristics of the septide-sensitive binding sites (labeled with [125I]NKA) largely differ from those of classic NK1 binding sites, as determined on crude synaptosomes from the rat brain using [125I]Bolton-Hunter substance P (SP) as ligand. Indeed, several tachykinins including neurokinin A (NKA), neuropeptide K (NPK), neuropeptide gamma (NKgamma), and neurokinin B, as well as some SP and NKA analogues or C-terminal fragments such as septide, ALIE-124, SP(6-11), NKA(4-10), which have a weak affinity for classic tachykinin NK1 binding sites exhibited a high affinity for the septide-sensitive binding sites. In contrast, SP, classic selective NK1 agonists, and antagonists had a high affinity for both types of binding sites. The presence of a large population of tachykinin septide-sensitive binding sites in the rat submaxillary gland may thus explain why NPK and NPgamma induce salivary secretion and may potentiate the SP-evoked response in spite of the absence of tachykinin NK2 receptors in this tissue.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U114, Collège de France, Paris.
authors.forename: J C
authors.initials: JC
authors.lastname: Beaujouan
authors.forename: M
authors.initials: M
authors.lastname: Saffroy
authors.forename: Y
authors.initials: Y
authors.lastname: Torrens
authors.forename: S
authors.initials: S
authors.lastname: Sagan
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
mesh_terms: D000818:Animals; D001665:Binding Sites; D007457:Iodine Radioisotopes; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*; D015320:Tachykinins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; D015320:Tachykinins