Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cDNA clones for NK-2 receptors (NK-2R) were isolated from guinea-pig lung (GPl) and rabbit pulmonary artery (Rpa) using a polymerase chain reaction based methodology. The GPl NK-2R consists of 402 amino acids and encodes a protein with a relative molecular mass of 45,097. The Rpa NK-2R consists of 384 amino acids and encodes a protein with a relative molecular mass of 43,169. The GPl and Rpa NK-2Rs share significant amino acid sequence homology amongst themselves (90.1%), as well as with human, bovine, hamster and rat NK-2 receptors. The two receptors were stably transfected into mouse erythroleukemia cells, high-speed membranes were prepared from induced cells and their pharmacological properties examined utilizing [3H]-NKA in a receptor-binding assay. [3H]NKA bound to both NK-2Rs with high affinity (KD = 2-7 nM) and saturable (Bmax = 633-9000 fmol/mg protein) manner which was inhibited by GTP analogs. Competition experiments with agonists demonstrated identical order of potency in both NK-2Rs; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) > > Substance P > > > Senktide. Similarly, an identical profile for both receptors was observed with selective NK-2 antagonists: SR48,968 > MEN10,376 > > R396. The rank order of antagonist affinity is consistent with that in cloned human NK-2R and the observations of NK-2 receptor pharmacology in native human, guinea pig and rabbit tissues.
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PMID:Isolation and characterization of neurokinin A receptor cDNAs from guinea-pig lung and rabbit pulmonary artery. 867 25

Functional cDNA clones for hamster neurokinin-2 receptor (NK-2R) were isolated from hamster urinary bladder using a polymerase chain reaction-based methodology. The hamster NK-2R consists of 384 amino acids with a relative molecular weight of 43,418. Hamster NK-2R shares significant amino acid sequence homology with other tachykinin receptors, particularly with rat, bovine, and human NK-2R (94.3, 84.4, and 86.5%, respectively). To examine the pharmacology of cloned hamster NK-2R, we transfected mouse erythroleukemia cells with this receptor, prepared high speed membranes, and studied the receptor properties utilizing the ligand [4,5-3H-Leu9]NKA in a receptor-binding assay. For pharmacological comparison, we also transfected the human NK-2R into mouse erythroleukemia cells. [3H]NKA bound to hamster NK-2R receptor in a protein-dependent, high affinity (Kd1 = 4.14 +/- 0.31 nM), saturable (Bmax1 = 679 +/- 26 fmol/mg of protein), and highly specific manner (89 +/- 2%). A smaller population (10% density) of lower affinity receptors (Kd2 = 150 +/- 92 nM), was also observed in competition experiments. [3H]NKA bound to the human receptor with significantly higher affinity and overall greater receptor density (Kd1 = 0.37 +/- 0.11 nM, Bmax1 = 234 +/- 175 fmol/mg of protein; Kd2 = 9.0 +/- 2 nM, Bmax2 = 1989 + 990 fmol/mg of protein). [3H]NKA binding to both hamster and human receptors was enhanced greatly by divalent cations, whereas GTP analogs weakly inhibited binding to hamster receptor, but potently inhibited binding to the human receptor. Competition experiments with agonists demonstrated binding to high and low affinity states of NK-2 receptors, with identical order of potency in hamster or human NK-2R; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) >> substance P >>> Senktide. However, remarkable differences were observed in studies with selective NK-2 antagonists (hamster, SR48,968 > L659,877 > R396 >> MEN10,376 versus human, SR48,968 > MEN10,376 > L659,877 > R396). The rank order of antagonist affinity is consistent with the observations of NK-2 receptor pharmacology in the native tissues.
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PMID:Isolation and pharmacological characterization of a hamster urinary bladder neurokinin A receptor cDNA. 830 85