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)

Adenosine receptors capable of modulating tachykininergic transmission were characterized in functional studies using both field-stimulated and cholecystokinin octapeptide-stimulated contractile responses of atropinized guinea pig longitudinal muscle-myenteric plexus preparations. These tetrodotoxin-sensitive responses, which were mediated by release of one or more tachykinins, were inhibited by adenosine analogs in a concentration-dependent manner. The rank order of potencies of the analogs as inhibitors of the responses to cholecystokinin octapeptide was N6-cyclopentyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than 2-phenylaminoadenosine (CV 1808). Schild analysis of the antagonism of the presynaptic inhibitory effects of 5'-N-ethylcarbocamidoadenosine and N6-cyclopentyladenosine on cholecystokinin octapeptide-stimulated responses using the A1 selective antagonists 1,3-dipropyl-8-(4-sulfophenyl)xanthine and 1,3-dipropyl-8-(cyclopentyl)xanthine yielded linear isoboles with unit slopes indicating competitive antagonism. The affinity of the antagonists for the receptor site(s) involved in inhibition of tachykininergic transmission was similar to those established previously for cholinergic transmission. The rank order of potency of adenosine analogs as inhibitors of the field-stimulated responses was such that N6-cyclopentyladenosine = 5'-ethylcarboxamidoadenosine. Reverse-phase high-performance liquid chromatography analysis performed on lysates of isolated myenteric nerve endings demonstrated the presence of substance P and neurokinin-A. Neurokinin-B was undetectable. These studies indicate that adenosine receptor(s) on myenteric nerve endings are coupled negatively to tachykinin release and that they are probably identical to those involved in the modulation of acetylcholine release.
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PMID:Adenosine receptors are coupled negatively to release of tachykinin(s) from enteric nerve endings. 169 84

Substance P (SP) is one of the endogenous tachykinin peptides implicated in neurogenic inflammation and may be critically involved in diseases as diverse as asthma, arthritis and inflammatory bowel disease. The current study was initiated to identify a rich source of SP receptor that would be amenable for studying the regulatory mechanism of the receptor. By using a radioligand receptor binding technique, sheep ileal smooth muscle membranes showed a much higher density of [3H]SP specific binding than other non-neural rat or sheep tissues and organs surveyed. Of the protease inhibitors tested, only phosphoramidon, a specific and potent enkephalinase inhibitor, prevented the degradation of [3H]SP and enhanced [3H]SP binding to the membrane. [3H]SP binding to the specific binding sites in the membranes was time-dependent and reached a steady state after 60 min at 22 degrees C in 25 mM Tris.NH3 (pH 7.4). Calcium and magnesium ions enhanced [3H]SP specific binding. Saturation binding studies showed that the dissociation constant (KD) and the density of maximum binding sites for [3H]SP specific binding were 0.54 nM and 83 fmol/mg of protein, respectively. The specificity of the [3H]SP labeled sites was SP greater than (4-11) SP greater than eledoisin greater than spantide greater than neurokinin-A greater than D-Pro2D-Phe7D-Trp9-SP. Neurokinin-B and senktide showed no inhibition of [3H]SP binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification and characterization of the substance P receptor in sheep intestinal smooth muscle membranes. 169 67

The interactions between IL-1 and several neuropeptides associated with pain and inflammation were examined in the context of fibroblast proliferation as a paradigm for the synovial hyperplasia associated with chronic rheumatoid arthritis. The BALB/3T3 fibroblast cell line, which proliferates in response to increasing doses of IL-1, demonstrated enhanced proliferation after a 72-h culture period when various neuropeptides were included with IL-1 in serum-free medium. Thus, bradykinin, at concentrations between 10(-8) and 10(-5) M, moderately promoted [3H]TdR incorporation in vitro in the BALB/3T3 cells, and substance P at approximately 3 x 10(-9) to 3 x 10(-7) M demonstrated minor proliferative activity. However, when the cells were cultured with IL-1 plus substance P or IL-1 plus BK, the ensuing proliferative responses, as measured by [3H]TdR incorporation, were consistently magnified greater than or equal to twofold above the anticipated additive response caused by IL-1 in combination with either of those neuropeptides. Combinations of IL-1 and SP, or IL-1 and BK, also provoked increases in cell numbers that did not occur when the mediators were tested individually. In other experiments, we tested neurokinin-A, Neurokinin-B, histamine, and serotonin. These results are discussed with respect to neurogenic contributions to the immunopathology of IL-1-mediated inflammation.
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PMID:Potentiation of IL-1-induced BALB/3T3 fibroblast proliferation by neuropeptides. 246 86

The purpose of the study was to compare in vitro airway responses to neurokinin A & B (NKA and NKB) and expression of NK-2 receptors in airways of horses affected and unaffected with recurrent airway obstruction (RAO). Neurokinin-A, an inflammatory mediator belonging to the tachykinin family of neuropeptides, causes bronchoconstriction by binding to NK-2 receptors. Neurokinin-B is a lesser-known neuropeptide that acts on NK-3 receptors. Horses were placed into RAO-affected and RAO-unaffected groups based on their history, clinical scoring, and pulmonary function testing. Lung tissue from each lobe was collected for immunohistochemical staining for NK-2 receptors. Cumulative concentration-response relationships were determined on bronchial rings (4-mm wide) collected and prepared from the right diaphragmatic lung lobe to graded concentrations (half log molar concentrations 10(-7)M to 10(-4)M) of NKA and NKB. The results showed that NKA caused significantly greater contraction than NKB in both groups. In RAO-affected horses, both agents produced significantly greater bronchial contractions than those in the RAO-unaffected horses. Immunohistochemical staining showed that the overall NK-2 receptor distribution was significantly increased in bronchial epithelium and smooth muscles of bronchi and pulmonary vessels of RAO-affected than RAO-unaffected horses. The findings indicate that NK-2 receptors are up-regulated in RAO, suggesting that NK-2 receptor antagonists may have some therapeutic value in controlling the progression of airway hyperreactivity in horses affected with RAO.
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PMID:Neurokinin receptors in recurrent airway obstruction: a comparative study of affected and unaffected horses. 1933 92

The tachykinin neurokinin B which is encoded on the tachykinin 3 precursor, has prominent roles in both neuronal and endocrine systems, yet little is known about its evolution, potential splice variants and the manner in which it is processed. Here, we deduce the diversity within the vertebrate tachykinin 3 precursors, and identify novel tachykinin 3 splice variants and precursors. A total of 35 different tachykinin 3 precursors were identified in mammals, birds and reptiles. Nine additional alternatively spliced tachykinin 3 mRNA transcripts were also discovered in humans leading to the formation of three tachykinin 3 precursors (named alpha, beta and gamma tachykinin 3), but no novel tachykinin. gamma tachykinin 3, albeit rarer, was not found to encode neurokinin B. Differential processing of the tachykinin 3 precursor in the human placenta leads to the formation of potential NH2-terminally extended forms of neurokinin B. Moreover, we found increased proteolytic cleavage of the tachykinin 3 precursor during the pregnancy syndrome of pre-eclampsia. We have established neurokinin B to be an evolutionarily conserved peptide, nonetheless the significance of the three different tachykinin 3 precursors is not clear, but could represent an evolutionarily redundant splicing mechanism once employed by an ancestral gene that encoded two tachykinins. Our results indicate that differential mRNA splicing and precursor processing is likely to play an important role in differentiating the actions of the tachykinin 3 gene products in both neuronal and endocrine tissues.
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PMID:Differential mRNA splicing and precursor processing of neurokinin B in neuroendocrine tissues. 1943 24