Human substance P receptor (NK-1): organization of the gene, chromosome localization and functional expression of cDNA clones

Abstract

The gene for the human substance P receptor (NK-1) was cloned using cDNA probes made by the polymerase chain reaction from primers based on the rat sequence. The gene spans 45-60 kb and is contained in five exons, with introns interrupting at sites homologous to those in the NK-2 receptor gene. Analysis of restriction digests of genomic DNA from mouse/human cell hybrids indicates the NK-1 receptor is a single-copy gene located on human chromosome 2. Polymerase chain reaction using primers based on the 5' and 3' ends of the coding sequence was used to generate full-length cDNAs from human lung and from IM9 lymphoblast cells. When transfected into COS-7 cells, the NK-1 receptor binds 125I-BHSP with a Kd of 0.35 +/- 0.07 nM and mediates substance P induced phosphatidylinositol metabolism. The receptor is selective for substance P; the relative affinity for neurokinin A and neurokinin B is 100- and 500-fold lower, respectively. Human IM9 lymphoblast cells express relatively high levels of the NK-1 receptor, and Northern blot analysis indicates modulation of mRNA levels by glucocorticoids and growth factors, suggesting that this cell line may be useful as a model for studying the control of NK-1 receptor gene expression.

Therapeutic Innovations for Targeting Hepatoblastoma

“…In its full-length form, NK1R is a protein of 417 amino acids (80). It belongs to the class I of GPCRs and can be coupled to several groups of G proteins: the Gαq, Gαs and the Gαi (81,82).…”

Demonstration of the Efficacy and Safety of a Novel Substance P (NK1) Receptor Antagonist in Major Depression

“…It has been shown that limbic binding sites for SP are colocalized with those of monoamine neurotransmitters (Dietl and Palacios, 1991;Elliot et al, 1986;Gerard et al, 1991;Hershey and Krause, 1990;Hökfelt, 1991;Hopkins et al, 1991;Masu et al, 1987;Takeda and Krause, 1991;Yokota et al, 1989). SP displays highest affinity for tachykinin, type 1 [NK 1 ] receptors (Otsuka and Yoshioka, 1993).…”

Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor

“…The human NK1R gene (2)(3)(4)(5), localized to chromosome 2, has been cloned. NK1R is a member of the G protein-coupled receptor (GPCR) superfamily and has a structure of seven transmembrane domains, an extracellular amino terminus and an intracellular carboxyl terminus (2).…”