Cloning and expression of a rat neuromedin K receptor cDNA Journal Article


Author(s): Shigemoto, Ryuichi; Yokota, Yoshifumi; Tsuchida, Kunihiro; Nakanishi, Shigetada
Article Title: Cloning and expression of a rat neuromedin K receptor cDNA
Affiliation
Abstract: Functional cDNA clones for rat neuromedin K receptor were isolated from a rat brain cDNA library by cross-hybridization with the bovine substance K recepor cDNA. Injection of the mRNA synthesized in vitro from the cloned cDNA into Xenopus oocytes elicited electrophysiological responses to tachykinins, with the most potent sensitivity being to neuromedin K. Ligand-binding displacement in membranes of mammalian COS cells transfected with the cDNA indicated the rank order of affinity of the receptor to tachykinins; neuromedin K > substance K > substance P. The hybridization analysis showed that the neuromedin K receptor mRNA is expressed in both the brain and the peripheral tissues at different levels. The rat neuromedin K receptor consists of 452 amino acid residues and belongs to the family of G protein-coupled receptors, which are thought to have seven transmembrane domains. The sequence comparison of the rat neuromedin K, substance P, and substance K receptors revealed that these receptors are highly conserved in the seven transmembrane domains and the cytoplasmic sides of the receptors. They also show some structural characteristics, including the common presence of histidine residues in transmembrane segments V and VI and the difference in the numbers and distributions of serine and threonine residues as possible phosphorylation sites in the cytoplasmic regions. This paper thus presents the first comprehensive analysis of the molecular nature of the multiple peptide receptors that exhibit similar but pharmacologically distinguishable activities.
Keywords: unclassified drug; Receptor; neurokinin B; complementary dna; peptide receptor
Journal Title: Journal of Biological Chemistry
Volume: 265
Issue 2
ISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1990-01-01
Start Page: 623
End Page: 628
Open access: no