Disease relevance of Neurokinin alpha

• C6-2B rat glioma cells were stably transfected with substance K receptor cDNA and used to study interactions between cAMP and Ca2+ signaling pathways [1].
• Phosphodiesterase inhibitors, down-regulation or inhibition of protein kinase C, and pertussis toxin failed to prevent substance K-induced inhibition of agonist-stimulated cAMP accumulation [1].
• Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease [2].
• The tachykinins SP and NKA, released from terminals of primary sensory neurons in peripheral tissues, cause all the major signs of inflammation (neurogenic inflammation) by means of activation of NK(1) and NK(2) receptors [3].
• In this study, high levels of CPH activity was found in a liver metastasis of a human ileal carcinoid which expresses beta-preprotachykinin mRNA and the tachykinin neuropeptides, substance P and substance K [4].

High impact information on Neurokinin alpha

• Identified examples include the mammalian opsins, alpha 1-, alpha 2-, beta 1- and beta 2-adrenergic receptors, the muscarinic receptor family, the 5-HT1C-receptor, and the substance-K receptor [5].
• Mammals contain three distinct tachykinin neuropeptides, substance P, substance K and neuromedin K, and it has been suggested that there are multiple tachykinin receptors [6].
• cDNA cloning of bovine substance-K receptor through oocyte expression system [6].
• Stimulation of connective tissue cell growth by substance P and substance K [7].
• We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide [7].

Biological context of Neurokinin alpha

• Alternative RNA splicing generates two distinct mRNAs encoding the neuropeptide substance P alone or with substance K from a single preprotachykinin gene [8].
• We identified clones encoding a Drosophila receptor for tachykinin-like peptides by low stringency screening of an embryonic cDNA library with probes from the bovine substance K receptor [9].
• This paper describes the amino acid sequence of the rat substance P receptor and its comparison with that of the rat substance K receptor on the basis of molecular cloning and sequence analysis [10].
• The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of the cDNA from tracheal and gastric tissues [11].
• We have previously demonstrated that the neuropeptide, neurokinin A (NKA) (substance K), causes bronchoconstriction in subjects with asthma [12].

Anatomical context of Neurokinin alpha

• In intestinal smooth muscle and bladder, however, labeled substance K and labeled eledoisin were both bound in a pattern indicating a preference for substance K itself [13].
• Substance P, substance K, and the carboxyl-terminal peptide SP(4-11) induce the release of interleukin-1, tumor necrosis factor-alpha, and interleukin-6 from human blood monocytes [14].
• This receptor binding site is labeled by Bolton-Hunter conjugates of NK, SK, eledoisin, or kassinin and is found in high concentrations in laminae 4 and 5 of the cerebral cortex, the ventral tegmental area, laminae 1 and 2 of the spinal cord, and the inner plexiform layer of the retina [15].
• This receptor binding site is labeled by SK, eledoisin, or kassinin radioligands and tissues that express high concentrations include the muscularis mucosae of the esophagus, the circular muscle of the colon, and the external muscle of the bladder [15].
• Rat genomic clones were used to quantitate preprotachykinin mRNAs in the rat basal ganglia, while the tachykinin peptide products substance P and substance K were measured by radioimmunoassay [16].

Associations of Neurokinin alpha with other chemical compounds

• The Ca2+ rise in oocytes induced by substance K was due to internal Ca2+ mobilization and was independent of external Ca2+, since it occurred in Ca2(+)-free medium fortified with 2 mM EGTA [17].
• Physalaemin was a more potent inhibitor of binding than SP, whereas kassinin, eledoisin, and neurokinin A (substance K, neuromedin alpha, or neurokinin L) were much less potent [18].
• In competitive displacement studies, the order of potency of analogs for inhibition of the saturable binding of radiolabeled substance P to chief cells was substance P = physalaemin greater than substance K greater than neuromedin K; thus, the chief cell has a substance P-preferring tachykinin binding site [19].
• Replacement of Gly166 and Tyr167 in this epitope of the substance P receptor by the corresponding substance K receptor amino acids (Cys and Phe) increases the affinity toward substance P 2-fold and toward substance K and neurokinin B 11- and 21-fold, respectively [20].
• Neither NPS 467 nor 568 affected ICl in water-injected oocytes or in oocytes expressing the substance K receptor or the metabotropic glutamate receptor 1a [21].

Gene context of Neurokinin alpha

• Immunoblot analysis revealed that SK elicited a parallel increase in TH enzyme protein [22].
• However, results of in situ hybridization experiments intimated that eosinophils produced predominantly preprotachykinin mRNAs which encode SP but are devoid of the SK/neuropeptide K sequence [23].
• Sequencing analysis of the PCR products from bovine hypothalamus, mouse brain, and human testis confirmed the structure of these transcripts, which encode both substance-P and neurokinin-A (substance-K) neuropeptide hormones [24].
• Novel pharmacology of substance K-binding sites: a third type of tachykinin receptor [13].
• Functional cDNA clones for rat neuromedin K receptor were isolated from a rat brain cDNA library by cross-hybridization with the bovine substance K receptor cDNA [25].

Analytical, diagnostic and therapeutic context of Neurokinin alpha

• These data fit well with radioimmunoassay data that suggest that, whereas in the CNS SP, SK and NK are present in high concentrations, in peripheral tissues only SP and SK are present in detectable concentrations [15].
• In this study, reverse-phase HPLC was used to fractionate peptides in bovine adrenal medullary extracts, and the fractions were analyzed by radioimmunoassay using antisera to SP or neurokinin A (NKA) [26].
• Binding sites for the [125I]Bolton-Hunter-labeled tachykinins substance K (BHSK), eledoisin (BHE) and substance P (BHSP) were investigated using crude membrane suspensions and autoradiography [27].
• Thus, in this preparation CGRP rather than a neurokinin (SP/NKA) is responsible for the capsaicin-induced dilatations [28].
• The regional distribution of 3 mammalian tachykinins (substance P, neurokinin alpha and neurokinin beta) in the rat spinal cord and related structures was investigated using a method of radioimmunoassay combined with high performance liquid chromatography [29].

References