Patent ID: 7972800

Claim:
A method of screening a compound or a salt thereof that changes the binding property or signal transduction of a G protein-coupled receptor protein comprising the amino acid sequence represented by SEQ ID NO: 1, SEQ ID NO: 6 or SEQ ID NO: 8, or a salt thereof, to an ionizable metal element or a salt thereof, comprising: (A) (i) bringing the protein in contact with the ionizable metal element, (ii) bringing the protein in contact with the ionizable element and a test compound or its salt, (iii) assaying a binding amount of the ionizable metal element to the protein for both (i) and (ii), (iv) comparing the binding amount of the ionizable metal element between (i) and (ii), and (v) obtaining the test compound that changes the binding amount of the metal element, wherein the ionizable metal element is selected from the group consisting of cobalt, nickel, copper, zinc or cadmium, (B) (i) bringing the protein in contact with an ionizable metal element, (ii) bringing the protein in contact with the ionizable metal element and a test compound or its salt, (iii) measuring a cell-stimulating activity of the protein for both (i) and (ii), and (iv) comparing the cell-stimulating activities between (i) and (ii), wherein the method of screening is a method of screening for an agonist or an antagonist to said G protein-coupled receptor protein or salt thereof, wherein the ionizable metal element is selected from the group consisting of cobalt, nickel, copper, zinc or cadmium, wherein said cell-stimulating activity is selected from the group consisting of the activities that promote or suppress arachidonic acid release, acetylcholine release, intracellular Ca 2± release, intracellular cAMP production, intracellular cGMP production, inositol phosphate production, cell membrane potential, phosphorylation of intracellular proteins, activation of c-fos, pH reduction, and promoting the secretion of cytokines from GPR39 expression cell UM-UC-3, and wherein the test compound or its salt that increases the cell-stimulating activity is an agonist of the G-protein coupled receptor protein, and the test compound or its salt that decreases the cell-stimulating activity is an antagonist for the G-protein coupled receptor protein, or (C) assaying an intracellular Ca 2+ level increasing activity (i) when a test compound or a salt thereof and an ionizable metal element is brought into contact with a cell containing said receptor protein, and (ii) when the ionizable metal element is brought in contact with a cell containing said receptor protein, and comparing the intracellular Ca 2+ level increasing activity between (i) and (ii), wherein the method of screening is a method of screening an agonist for said G protein- coupled receptor protein or salt thereof, wherein the ionizable metal element is selected from the group consisting of cobalt, nickel, copper, zinc or cadmium, wherein the test compound that has the intracellular Ca 2+ level increasing activity is an agonist.