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)

The effects of inhaled bradykinin (BK), substance P (SP), and neurokinin A (NKA) on pulmonary resistance and airway responsiveness to carbachol were studied in conscious allergic sheep. Inhaled BK (20 breaths, 0.1 to 5.0 mg.ml-1) caused dose-dependent increases in pulmonary resistance. Neither inhaled SP nor NKA (20 breaths, 0.1 to 1.0 mg.ml-1) produced significant bronchoconstriction in allergic sheep. However, the response to SP could be enhanced (p less than 0.05) by pretreatment with the neutral endopeptidase inhibitor, thiorphan (40 breaths, 1 mg.ml-1). Sheep that were allergic to Ascaris suum antigen were 5.9 times (p less than 0.05) more sensitive to the constrictor effects of BK than nonallergic sheep. BK-induced bronchoconstriction was blocked in a dose-dependent fashion by the BK beta 2-receptor antagonist, NPC 567 (D-arginine[hydroxyproline3,D-phenylalanine7]BK). Atropine (0.2 mg.kg-1, intravenously) and nedocromil sodium (1 mg.kg-1 in 3 ml of saline, aerosolized) significantly inhibited the BK-induced bronchoconstriction by 97% and 43%, respectively. Chlorpheniramine (2 mg.kg-1, intravenously) had no effect. NKA caused a transient increase in airway responsiveness in allergic sheep, producing a mean 1.9-fold leftward shift in dose-response curves to aerosolized carbachol (p less than 0.05). This hyperresponsiveness was not evident 24 hours after NKA challenge. Neither SP nor BK changed airway responsiveness. Thus, in allergic sheep, inhaled BK caused a more pronounced bronchoconstriction than that observed in nonallergic sheep. The bronchoconstriction was blocked by a BK-receptor antagonist and appeared to be partially mediated via cholinergic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. 170 88

The objective of our study was to determine whether the pure synthetic substance P(SP) is algesiogenic or analgesic when administered centrally or peripherally. The relationships between SP-induced analgesia and the content of morphine-like factor (MLF) in the brain were also studied. Intracarotid arterial administration of SP (20-200 microgram) produced no pseudoaffective responses to pain in six out of nine rats, but in the remaining three, there was an exhibition of these responses. Chlorpheniramine pretreatment antagonized these responses. On cantharidin blister base experiments in humans, SP (10(-3) g/ml) produced slight pain and an itchy sensation. SP given intracerebroventricularly produced an analgesia in mice in a dose of 5 ng/mouse, as determined by the acetic acid-induced writhing and hot plate methods. These SP-induced analgesia were antagonized by naloxone pretreatment. SP did not alter the content of MLF in the mouse whole brain. However, SP5-11 not only produced an analgesia but also increased the content of MLF. These results suggest that SP has a slight algesiogenic activity which might be mediated by histamine and a slight analgesic activity which might be mediated by MLF.
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PMID:Algesiogenic and analgesic activities of synthetic substance P. 617 65

Substance P is present in sensory nerves in the lung and we report here its actions on the lung strip. Substance P was shown to produce rapid, small contractions of trhe lung strip at doses from 10(-9) to 10(-5) M, and there was no apparent dose-response relationship. In the presence of a mixture of three inhibitors of substance P breakdown: bacitracin, 1,4-dithio-L- threitol and ethylenediaminetetra-acetic acid all at 10(-4) M, the responses to substance P were greatly increased and dose-response curves could be established. The concentrations producing half maximal effect in the presence of these inhibitors were 6 X 10(-6) M +/- 4 X 10(-6) M. The inhibitors of substance P breakdown were found to have no effect on the histamine dose-response curve: any small shifts obtained were not significant. Chlorpheniramine 10(-6) M and 10(-5) M shifted the histamine dose-response curve to the right producing dose ratios of 100 and 900 respectively. At these doses chlorpheniramine had no effect on the dose-response curve to substance P. A dose of substance P not itself producing a response (5 X 10(-8) M) caused an increase in the size of the responses to histamine. The histamine dose-response curve was shifted to the left in the presence of substance P producing an average dose ratio of 1.4 +/- 0.2. In the presence of the peptidase inhibitors, dose-response curves have also been produced for physalaemin (10(-7) - 10(-5) M) and eledoisin (10(-7) - 10(-5) M).
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PMID:The effect of substance P and related peptides on the guinea-pig lung strip. 620 63

Electrical field stimulation (EFS) of guinea-pig airways, in vitro, evokes an excitatory nonadrenergic noncholinergic (eNANC) contraction mediated by release of tachykinins from sensory nerve endings. Epinastine (WAL 801CL) is an antihistaminic drug with binding affinity at certain other receptors, including alpha-adrenergic receptors and various serotonin (5-HT) receptor subtypes. It is used in asthma treatment; however, its mechanism of action remains to be fully defined. We have investigated whether epinastine could modulate the eNANC contraction in guinea-pig airways in vitro, and have tried to elucidate its receptor mechanism. Epinastine (0.1-100 microM) produced a concentration-dependent inhibition of the noncholinergic contraction, with a maximum inhibition of 91 +/- 7% at 100 microM. Pretreatment of the tissues with combined 5-HT1/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Chlorpheniramine (10 microM), another histamine H1 receptor antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM). These results suggest that epinastine, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.
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PMID:Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor. 883 55

The involvement of tachykinin receptors in skin inflammation induced by substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) was investigated in mouse ears. Intradermal injection of tachykinins (0.1-100 pmol/site) into the ear skin produced oedema formation. RP 67580 (ED50: 0.34 mg/kg, i.v.) and SR 140333 (ED50: 0.19 mg/kg, i.v.), the non-peptide NK1 receptor antagonists, inhibited SP-induced oedema. SR 140333 was also effective in preventing NKA- and NKB-induced oedema. SR 48968 (1 mg/kg, i.v.), a non-peptide NK2 antagonist, induced a significant inhibition of NKA-induced oedema but had no effect on the response to SP and NKB. SR 142801 (3 mg/kg, i.v.), a non-peptide NK3 antagonist, prevented only NKB-induced oedema. In contrast, phosphoramidon (0.1 and 0.5 mg/kg, i.v.), an endopeptidase inhibitor, enhanced the oedema response to tachykinins. SR 140333, SR 48968, and SR 142801 blocked the enhancement by phosphoramidon of the response to SP, NKA, and NKB, respectively. Plasma extravasation in ear skin was induced by i.v. injection of tachykinins (0.7-17.6 nmol/kg). RP 67580 (ED50: 0.15 mg/kg, i.v. for SP) and SR 140333 (ED50: 14.3 micrograms/kg, i.v. for SP) inhibited tachykinin-induced plasma extravasation in ear skin. However, SR 48968 and SR 140281 had no effect on the vascular response to tachykinins. Chlorpheniramine (4 mg/kg, i.v.), a histamine H1 blocker, inhibited the response to local SP but not to i.v. SP. These results suggest that in addition to the NK1 receptors, functional NK2 and NK3 receptors may participate in the oedema response to local NKA and NKB in the ear skin. However, it appears that NK1 receptors on blood vessels are involved predominantly in plasma extravasation induced by i.v. tachykinins in the ear.
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PMID:Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P, neurokinin A, and neurokinin B in mouse ear. 884 32