Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 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 role of airway inflammation, induced by weekly antigen challenge, in the airway hyperresponsiveness to vagal (whole and NANC components) nerve stimulation and to neurotransmitters (acetylcholine and selective agonists for tachykinin NK1 and NK2 receptors) has been studied in the guinea-pig. Primarily, the time course (3, 7 and 14 days following the last challenge) of the effects of repeated aerosol antigen challenge on airway inflammation and bronchoalveolar fluid cellular composition was investigated. At 7 days following the last antigen challenge a maximal (as compared to 3 and 14 days) inflammatory response, in terms of a diffuse mild to marked infiltration of eosinophils, neutrophils and lymphocytes, was evident throughout pulmonary tissues. Only at this time some evidence of eosinophilia and neutropenia was detectable in BAL fluids. In these animals there was a normal bronchial responsiveness to iv administration of acetylcholine, selective synthetic agonists for the tachykinin NK2 receptors and capsaicin. On the other hand a remarkable airways hyperresponsiveness to iv administration of selective agonists for tachykinin NK1 receptors, as well as electrical stimulation of the vagal nerves (in presence and in absence of atropine), was detected. As a whole, these data indicate that at the peak of the inflammatory airway response following multiple antigen challenge there is a selective hyperresponsiveness to stimulation of vagal (mainly the non-adrenergic, non-cholinergic component) nerves associated with an increase in tachykinins (NK-1)-mediated bronchospasm.
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PMID:Hyperresponsiveness to non-adrenergic, non-cholinergic vagal stimulation following multiple antigen challenge in guinea-pigs. 853 95