Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, Na-(tert-butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-azap++ + henylalanine 2-benzyloxyethylamide (TAC-363). In vitro studies showed that TAC-363 caused a rightward shift of the contraction response curve with a slight inhibition of maximal response for the neurokinin A (NKA)-induced contraction of the hamster trachea and parallel rightward shift of the curve for the substance P (SP)-induced contraction of the guinea-pig ileum. The pA2 values were 9.82 and 8.42 on the contraction by NKA and SP, respectively. The selectivity of TAC-363 to NK-2 receptor was 25 times higher than that to NK-1 receptor. The compound did not affect the histamine and acetylcholine-induced bronchoconstriction in guinea-pig ileum. Intravenous administration (0.1-1 mg/kg) of the compound inhibited dose-dependently both NKA- and capsaicin-induced bronchoconstriction in guinea-pigs. The inhibitory effect of the compound lasted up to 60 min on NKA-induced bronchoconstriction in guinea-pigs. These results suggest that TAC-363 is a potent and selective NK-2 receptor antagonist, which is effective in vitro and in vivo. It may be useful in the treatment of NKA-dependent pathology, especially bronchial asthma.
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PMID:[Pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, TAC-363]. 898 32

We examined the effect of a novel tachykinin NK-2-receptor antagonist, N alpha-(tert-Butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-aza- phenylalanine 2-benzyloxyethylamide (TAC-363), on hyperventilation- and citric acid-induced bronchoconstriction and neurokinin A (NKA)-, capsaicin- and antigen-induced airway hyperresponsiveness in guinea pigs. The i.v. administration of TAC-363 at doses of 0.01-1 mg/kg inhibited hyperventilation- and citric acid-induced bronchoconstriction in a dose-dependent manner, while FK-888, a tachykinin NK-1-receptor antagonist, did not inhibit hyperventilation-induced bronchoconstriction. NKA-induced airway hyperresponsiveness to acetylcholine was attenuated by i.v. injection of TAC-363, but not by the thromboxane A2 synthetase inhibitor ozagrel and the mast cell stabilizer DSCG. Furthermore, TAC-363 prevented the occurrence of capsaicin- and antigen-induced airway hyperresponsiveness to acetylcholine, while FK-888 did not prevent occurrence of capsaicin-induced airway hyperresponsiveness. In summary, TAC-363 inhibits bronchoconstriction and airway hyperresponsiveness induced by various stimuli. These results suggest that NKA mediates bronchoconstriction and airway hyperresponsiveness. Thus, TAC-363 is expected to be useful in the treatment of airway diseases such as asthma.
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PMID:[Effect of a novel tachykinin NK-2-receptor antagonist, TAC-363, on bronchoconstriction and airway hyperresponsiveness in guinea pigs]. 906 96

We analyzed tachykinin NK(3) receptor (NK(3)R) gene expression by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in uteri from young (3-month-old) and old (30-month-old) rats. In addition, we characterized the expression of the preprotachykinin-B (TAC-3) gene, which encodes neurokinin B (NKB), the preferred endogenous agonist of NK(3)R. Compared with young rats, NK(3)R messenger RNA (mRNA) levels were about 45-fold higher in uteri from old animals. TAC-3 mRNA was expressed in the rat uterus, and its levels were about 2.5-fold higher in old than in young rats. The contractile effect of the selective tachykinin NK(3)R agonist [MePhe(7)]-NKB in uteri from young and old animals was investigated by using conventional organ bath technique. A marked correlation was observed between the magnitude of the contraction elicited by [MePhe(7)]-NKB and the level of expression determined by RT-PCR for the NK(3)R. These observations are consistent with a role for the NKB/NK(3)R ligand-receptor pair in regulating uterine functions and support the existence of a link between estrogen and the NK(3)R/NKB activation pathway.
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PMID:Increase in neurokinin B expression and in tachykinin NK(3) receptor-mediated response and expression in the rat uterus with age. 1171 79

Hemokinin-1 (HK-1) is a peptide encoded by the preprotachykinin gene, TAC-4, and shares the hydrophobic carboxyl-terminal (C-terminal) region common to mammalian tachykinin peptides, such as substance P (SP). It is generally believed that C-terminal fragments of SP elicit an excitatory effect, while pretreatment with amino-terminal (N-terminal) fragments of SP inhibits the function of SP; however, there is no available information on HK-1. Therefore, to clarify the characteristics of C-terminal and N-terminal fragments of HK-1, HK-1 was divided into HK-1 (1-5) as the N-terminal fragment and HK-1 (6-11) as the C-terminal fragment based on the similarity of amino acids between HK-1 and SP. Intrathecal administration of HK-1 (6-11) induced scratching behavior similar to HK-1, while HK-1 (1-5) hardly induced scratching. Pretreatment with HK-1 (1-5), however, attenuated scratching induced by HK-1 and SP, whereas pretreatment with SP (1-5) attenuated SP-induced scratching, but not HK-1. Furthermore, intrathecal administration of HK-1 (1-5) and SP (1-5) markedly attenuated the induction of flinching and enhancement of c-Fos expression in the spinal cord following the intradermal administration of formalin, a noxious stimulant, while pretreatment with HK-1 (1-5), but not SP (1-5), markedly attenuated the induction of scratching behavior by subcutaneous administration of pruritic agents, such as serotonin or histamine. Taken together, these findings indicate that HK-1 (1-5) suppresses pruritic and nociceptive processing, while SP (1-5) suppresses nociceptive processing. Therefore, it is suggested that HK-1 (1-5) may be a useful tool for revealing pruritic processing and HK-1 may play a crucial role in pruritic processing.
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PMID:An amino-terminal fragment of hemokinin-1 has an inhibitory effect on pruritic processing in rats. 2424 1