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 NK 2 or NK 3 agonists or antagonists exhibited weak or no affinity for [ 125I]NKA binding sites. As indicated by K i values of several compounds, the pharmacological characteristics of the septide-sensitive binding sites (labeled with [ 125I]NKA) largely differ from those of classic NK 1 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 γ (NKγ), 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 NK 1 binding sites exhibited a high affinity for the septide-sensitive binding sites. In contrast, SP, classic selective NK 1 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 NPγ induce salivary secretion and may potentiate the SP-evoked response in spite of the absence of tachykinin NK 2 receptors in this tissue.