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)

Three receptors for the tachykinins, NK1, NK2, and NK3, have been defined pharmacologically and have been cloned. We previously demonstrated that in Fisher 344 (F344) rats neurokinin A (NKA) and substance P (SP) cause bronchoconstriction mainly by indirect mechanisms that involve both cholinergic nerves and mast cells. Preliminary results suggested that in a less responsive strain, the BDE strain, tachykinins did not activate airway mast cells. We have now compared in F344 and BDE rats the airway effects of the tachykinins SP and NKA with those of specific NK1 and NK2 receptor agonists and have studied the effect of potent and specific nonpeptide NK1 and NK2 receptor antagonists on NKA-induced airway effects. Lung resistance (RL) and serotonin in bronchoalveolar lavage fluid (BAL 5HT) were measured in anaesthetized, mechanically ventilated, rats. In contrast to F344 rats, BDE rats were less sensitive to SP and NKA challenge, and no subsequent increase in BAL 5HT was observed. In F344 rats, the specific NK1 receptor agonists, [Sar9, Met(O2)11]SP and Ac[Arg6,Sar9,Met(O2)11]SP(6-11), caused a dose-dependent bronchoconstriction and increase in BAL 5HT comparable to those of NKA and SP. The NK1 receptor agonists had no effect in BDE rats. The NK2 receptor agonist [beta Ala8]NKA(4-10) caused a small, dose-dependent increase in RL in the F344 as well as in the BDE rat, but it had no effect on BAL 5HT. The NK1 receptor antagonists RP 67580 and CP 96,345 significantly reduced the increase in RL and BAL 5HT caused by NKA in the F344 rat, but they had no effect on the NKA-induced bronchoconstriction in the BDE rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo characterization of the tachykinin receptors involved in the direct and indirect bronchoconstrictor effect of tachykinins in two inbred rat strains. 751 94

The contractile effect of substance P, neurokinin A, carbachol and serotonin (5-HT) on isolated Fischer 344 rat trachea was studied. Contractions of two distal tracheal rings were measured isometrically in a 2-ml organ bath. Cumulative concentration-response curves were obtained for carbachol (EC50 ring 1: 1.6 x 10(-7) M and ring 2: 2.2 x 10(-7) M) and for 5-HT (EC50 ring 1: 10.2 x 10(-7) M and ring 2: 10.5 x 10(-7) M). Non-cumulative administration of substance P and neurokinin A (10(-8) to 10(-5) M) caused a concentration-dependent contraction with an EC50 (x 10(-7) M) of 1.10 +/- 0.27 and 1.97 +/- 0.45 respectively. The maximal contraction was 32.6 +/- 2.5% (substance P) and 32.6 +/- 1.5% (neurokinin A) of the maximal contraction with carbachol. In contrast, neither substance P nor neurokinin A caused contraction of trachea from BDE rats. The tachykinin NK1 receptor agonist, Ac[Arg6, Sar9, Met(O2)11] substance P-(6-11), caused a concentration-dependent contraction with an EC50 (x 10-(-9) M) of 1.38 +/- 0.09 and a maximal effect of 25.5 +/- 2.1% of the maximal contraction with carbachol. The tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), had a small contractile effect at 10(-6) M (8.4 +/- 0.8% of the maximal contraction with carbachol) while the tachykinin NK3 receptor agonist, senktide, had no effect up to 3.3 x 10(-6) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tachykinins contract trachea from Fischer 344 rats by interaction with a tachykinin NK1 receptor. 753 33

Tachykinins released from sensory airway nerves have been shown to increase vascular permeability and plasma-protein extravasation (PPE) in rodent airways. We previously demonstrated that in Fisher (F344) rats, tachykinins cause bronchoconstriction mainly by indirect mechanisms involving the activation of NK1 receptor and mast cells, whereas in the less responsive BDE rats tachykinins have a direct NK2 receptor-mediated effect on bronchial smooth muscle. Using Evans blue dye as an intravascular marker, we demonstrated that F344 rats are hyperresponsive for the PPE induced by substance P (SP) and capsaicin. The NK1 receptor antagonist RP 67,580 reduced the neurogenic PPE in both strains, whereas the NK2 receptor antagonist SR 48,968 had no effect, indicating that only NK1 receptors are involved in the PPE. Pretreatment with the 5-HT antagonist methysergide decreased the neurogenic PPE in F344 rats but not in BDE rats. In F344 rats depleted of mast-cell mediators with compound 48/80, the SP-induced PPE was significantly reduced. Pretreatment with the H1 antagonist mepyramine and the H2 antagonist cimetidine caused a similar reduction in SP-induced PPE in main bronchi of both strains. Pretreatment with atropine, indomethacin, or the leukotriene antagonist ICI 198,615 did not affect the SP-induced PPE. In conclusion, neurogenic PPE in rat airways involves the activation of NK1 receptors. In F344 but not in BDE rats, an additional indirect mechanism involving 5-HT release and mast-cell activation participates in the neurogenic PPE.
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PMID:Characterization of neurogenic inflammation in the airways of two highly inbred rat strains. 852 Jul 39

Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoconstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains, F344 and BDE. BDE-rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE- and F344-rats is probably related to a higher number of A3-receptors on the airway mast cells of BDE-rats. In contrast, F344-rats have a higher airway responsiveness to tachykinins than BDE-rats. Tachykinins cause bronchoconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats they cause bronchoconstriction by a direct effect on airway smooth muscle via activation of NK2-receptors. Finally we also observed a difference between F344- and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsaicin. In F344-rats but not in BDE-rats mast cell activation and the release of 5-hydroxytryptamine is partly responsible for this plasma protein extravasation.
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PMID:Genetic control of indirect airway responsiveness in the rat. 859 Mar 45