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Substance P Parameter Assay ParameterTM Substance P Assay Catalog Number KGE007 Catalog Number SKGE007 Catalog Number PKGE007 For the quantitative determination of Substance P in cell culture supernates, serum, plasma, saliva, and urine. This package insert must be read in its entirety before using this product. For research use only. Not for use in diagnostic procedures. TABLE OF CONTENTS SECTION PAGE INTRODUCTION ....................................................................................................................................................................1 PRINCIPLE OF THE ASSAY ..................................................................................................................................................2 LIMITATIONS OF THE PROCEDURE ................................................................................................................................2 TECHNICAL HINTS ................................................................................................................................................................3 PRECAUTIONS ........................................................................................................................................................................3 MATERIALS PROVIDED & STORAGE CONDITIONS ..................................................................................................4 PHARMPAK CONTENTS ......................................................................................................................................................5 OTHER SUPPLIES REQUIRED ............................................................................................................................................5 SAMPLE COLLECTION & STORAGE ................................................................................................................................6 SAMPLE PREPARATION.......................................................................................................................................................6 REAGENT PREPARATION ....................................................................................................................................................7 ASSAY PROCEDURE .............................................................................................................................................................8 CALCULATION OF RESULTS ..............................................................................................................................................9 TYPICAL DATA ........................................................................................................................................................................9 PRECISION ............................................................................................................................................................................ 10 RECOVERY............................................................................................................................................................................. 10 LINEARITY ............................................................................................................................................................................. 10 SENSITIVITY ......................................................................................................................................................................... 11 SAMPLE VALUES ................................................................................................................................................................. 11 SPECIFICITY .......................................................................................................................................................................... 11 REFERENCES ........................................................................................................................................................................ 12 PLATE LAYOUT .................................................................................................................................................................... 13 Manufactured and Distributed by: USA R&D Systems, Inc. 614 McKinley Place NE, Minneapolis, MN 55413 TEL: 800 343 7475 612 379 2956 FAX: 612 656 4400 E-MAIL: [email protected] Distributed by: Europe | Middle East | Africa Bio-Techne Ltd. China Bio-Techne China Co., Ltd. 19 Barton Lane, Abingdon Science Park Unit 1901, Tower 3, Raffles City Changning Office, Abingdon OX14 3NB, UK 1193 Changning Road, Shanghai PRC 200051 TEL: +44 (0)1235 529449 TEL: +86 (21) 52380373 (400) 821-3475 FAX: +44 (0)1235 533420 FAX: +86 (21) 52371001 E-MAIL: [email protected] E-MAIL: [email protected] INTRODUCTION Substance P (SP, Neurokinin-1) is member of the tachykinin peptide family. It was first discovered in 1931 as a hypotensive and spasmogenic factor in extracts of equine brain and intestine (1, 2). The isolation, characterization, and sequencing of Substance P took place in the early 1970s (3-5). Human Substance P is processed from preprotachykinin α, β, γ, and δ isoforms that also generate other tachykinin family members Neuropeptide K, Neurokinin A, Neurokinin B, and Neuropeptide γ (6, 7). Signal sequence and other processing results in the active 1348 Da, 11 amino acid (aa) peptide: RPKPQQFFGLM. Studies of synthetic peptides have shown that Phe at position 7 and amidation at the C-terminus are crucial for function, and that a basic or neutral aa at position 5 and an aromatic aa at position 8 are selective for the NK1 receptor (8). The sequence of Substance P is identical across mammalian species. Alligator and avian species have a single conservative amino acid substitution at position 3. Homologs such as physalaemin are present in the skin of amphibians as defense proteins. Non-neuronal Substance P is present in the endocrine cells of the intestinal mucosa and may be the source of Substance P found in the blood. Tumor epithelial cells may express and store Substance P and other tachykinins. Neuronal tissue is the main source of Substance P, both in the central nervous system (many areas of the brain and spinal cord) and in primary sensory neurons (C-type fibers) in the gut, respiratory tract, blood vessels, urinary system, skin, and lymphoid organs (6). Substance P binds primarily to the neurokinin 1 receptor (NK1 receptor, Substance P receptor, tachykinin receptor 1), and with low affinity to the NK2 and NK3 receptors (6, 7). The NK1 receptor is a 407 amino acid, seven-transmembrane G-protein-coupled receptor that activates a phosphatidylinositol-calcium second messenger system. The NK-1 receptor has potential N-glycosylation sites at the N-terminus, an intermolecular disulfide bond (C105 to C180), and an S-palmitoylation site at C322. NK2 and NK3 receptors have similar structure but limited sequence identity. Substance P is secreted from primary sensory afferent neurons after stimulation through protease-activated receptor 2 (PAR2). Calcitonin gene-related peptide (CGRP) is often co- secreted and induces inflammation in concert with SP (9, 10). SP is traditionally considered a neurotransmitter that engages NK1 receptors on neurons in the dorsal horn, transmitting pain signals through the central nervous system (9). However, when genes for either preprotachykinin A or NK1 receptor are disrupted, mice show normal pain thresholds but blunted responses to higher intensity stimuli (11, 12). Response to Substance P depends on the target cell and includes inducing hypotension, tachycardia, release of inflammatory mediators, and other responses. Direct antimicrobial effects of Substance P have also been shown (13). The Parameter™ Substance P Immunoassay is a 3.5 hour competitive enzyme immunoassay designed to measure Substance P in cell culture supernates, serum, plasma, saliva, and urine. It contains a synthetically derived human Substance P peptide and has been shown to accurately quantitate this peptide. Results obtained using samples containing natural Substance P showed linear curves that were parallel to the standard curves obtained using the Parameter kit standards. These results indicate that this kit can be used to determine relative mass values for natural Substance P. www.RnDSystems.com 1 PRINCIPLE OF THE ASSAY This assay is based on the competitive binding technique in which Substance P present in a sample competes with a fixed amount of horseradish peroxidase (HRP)-labeled Substance P for sites on a mouse monoclonal antibody. During the incubation, the monoclonal antibody becomes bound to the goat anti-mouse antibody coated onto the microplate. Following a wash to remove excess conjugate and unbound sample, a substrate solution is added to the wells to determine the bound enzyme activity. The color development is stopped and the absorbance is read at 450 nm. The intensity of the color is inversely proportional to the concentration of Substance P in the sample. LIMITATIONS OF THE PROCEDURE • FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES. • The kit should not be used beyond the expiration date on the kit label. • Do not mix or substitute reagents with those from other lots or sources. • If samples generate values higher than the highest standard, further dilute the samples with calibrator diluent and repeat the assay. • Any variation in diluent, operator, pipetting technique, washing technique, incubation time or temperature, and kit age can cause variation in binding.
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