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)

Undeca - and octa-peptide analogues of substance P (SP), acting as antagonists in the guinea pig ileum, have been tested on the guinea pig trachea. The antagonistic properties of several octapeptides, particularly of [pro4, trp7 ,9,10,Phe11]SP-(4-11) have been confirmed, while the undecapeptides have been found to be potent stimulants of the trachea. The contractions of the guinea pig trachea in response several undecapeptides , particularly [pro2, trp7 ,9, Leu11 ]SP, undergo rapid tachyphylaxis, are significantly reduced in the presence of diphenhydramine and are not influenced by octapeptide antagonists of SP. These contractions appear to be due to the activation of tissue sites mediating the release of intramural histamine and different from SP receptors. On repeated applications, the stimulant effects of undecapeptides are eliminated and the compounds can be tested as antagonists. Undecapeptide antagonists have been found to be more potent against eledoisin and kassinin than against SP or physalaemin, while the octapeptides are equally active against the four homologues. Both undeca - and octa-peptides seem however to exert a competitive type of antagonism against all the SP-related peptides tested in the present study. Differences of antagonistic affinities have been interpreted as indicative of the existence of two different receptor types for SP and related peptides in the guinea pig trachea. The two receptors are blocked by the octapeptide antagonists, which are not discriminatory, while undecapeptides are particularly active on the receptor subtype which shows high sensitivity for eledoisin and kassinin .
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PMID:Undeca- and octa-peptide antagonists for substance P, a study on the guinea pig trachea. 620 66

Following irritation of the airway, the ciliostimulatory effects of the tachykinin, substance P (SP), are thought to be secondary to mucus release. We hypothesized that SP also induces small increases in ciliary beat frequency (CBF) via a calcium-mediated process. Brushed ciliated cells from the nasal epithelium of healthy human subjects were suspended in tissue culture fluid and the acute effects of SP upon these cells were studied in a mucus-free environment. In some preparations, changes in CBF in response to SP were measured with a video-based system. The effect of an SP antagonist, of Ca2+ channel block with verapamil, and of the calcium analogue lanthanum on the SP response were also tested. In other preparations, the ciliated cells were preloaded with Fura-2, a dye which fluoresces with Ca2+ ions, and the response of intracellular Ca2+ to SP was monitored. SP (10(-9)-10(-6) M) transiently increased CBF in a dose-dependent manner, with the maximal response occurring at 10 min. The response was small, with a maximum increase of 8.9%. The SP receptor antagonist (D-pro2,D-trp7,9)-SP (10(-5) M) abolished this effect. Verapamil (10(-5) M) attenuated the response to SP (10(-7) M), whilst lanthanum chloride (250 microM) abolished it. Inhibition of SP destruction by phosphoramidon (10(-6) M) also eliminated the transient rise in CBF. However, compared to SP alone, the combination of SP and phosphoramidon induced a novel delayed lanthanum-sensitive rise in CBF. In other experiments, SP (10(-7) M) induced a transient increase in free intracellular Ca2+ concentration (maximal rise 73%), which returned to baseline before the expected onset of the CBF response. We conclude that substance P induces either a transient or sustained increase in CBF dependent on the rate of destruction of this peptide around tachykinin receptors. These receptors are likely to be linked to lanthanum- and verapamil-sensitive pathways for the entry of Ca2+ into cells. The small magnitude of the rise in CBF makes its physiological role uncertain at present.
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PMID:Interaction between calcium, neutral endopeptidase and the substance P mediated ciliary response in human respiratory epithelium. 883 39


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