UMLS:C0010200 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Comparisons were made between the doses required of aerosol and intraperitoneally administered morphine, dextromethorphan, codeine and the specific peripherally acting mu-receptor agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) to suppress citric acid-induced coughing in conscious guinea pigs. 2. Estimated ID50s for inhibition of numbers of coughs induced by an aerosol of 5% citric acid were 1.0 and 2.4 mg/kg for intraperitoneally administered morphine and dextromethorphan, respectively. 3. The estimated ID50s after inhalation of morphine and dextromethorphan as aerosols were approximately 2.2 and approximately 12 micrograms/kg, respectively. 4. Aerosilized codeine (approximately 72 micrograms/kg, n = 5) significantly inhibited coughing by 62 +/- 23% whereas 3 mg/kg, i.p. was required to significantly reduce coughing by a similar degree (60 +/- 6%, n = 7). 5. Inhalation of DALDA (approximately 7.2 micrograms/kg, n = 7) also significantly inhibited coughing. 6. The antitussive effect of inhaled morphine (approximately 7.2 micrograms/kg, n = 11) was inhibited after administration of 3 mg/kg of either naloxone hydrochloride or naloxone methylbromide intraperitoneally. 7. The results support the hypothesis that effects at a peripheral site can make a major contribution to the antitussive actions of these drugs.
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PMID:Evidence for peripheral mechanisms mediating the antitussive actions of opioids in the guinea pig. 181 Aug 7

1. Antitussive, antinociceptive and respiratory depressant effects of codeine, morphine and H.Tyr.D-Arg.Gly.Phe(4-NO2) Pro.NH2 (compound BW443C) were investigated in unanaesthetized guinea-pigs. Antagonism of the antitussive and antinociceptive effects was investigated by the use of nalorphine and N-methylnalorphine. Naloxone was used to antagonize respiratory depression. 2. Antitussive ED50s (with 95% confidence limits) for inhibition of cough induced by citric acid vapour were for codeine, morphine and BW443C respectively, 9.1(5.8-15), 1.3(0.7-2.4) and 1.2(0.6-2.6) mg kg-1 s.c. and 8.7(4.2-12), 1.6(1.2-1.9) and 0.67(0.002-3.3) mg kg-1, i.v. The antitussive effects of subcutaneous codeine (25 mg kg-1) morphine (8.1 mg kg-1) and BW443C (2.5 mg kg-1) were significantly antagonized by subcutaneous nalorphine (3.0 mg kg-1) and N-methylnalorphine (3.0 mg kg-1). 3. In the multiple toe-pinch test, the antinociceptive ED50s (with 95% confidence limits) of codeine and morphine were 18(16-22) and 2.3(0.4-4.3) mg kg-1, s.c., respectively. Compound BW443C was ineffective in doses of 2.5 and 10 mg kg-1 s.c., a result consistent with its lacking penetration into the CNS. Subcutaneous nalorphine (3.0 mg kg-1) antagonized the antinociceptive action of codeine (25 mg kg-1) and morphine (8.1 mg kg-1). In contrast, N-methylnalorphine (3.0 mg kg-1) had no significant effect on the antinociceptive action of codeine and morphine, suggesting lack of penetration of the CNS by N-methylnalorphine. 4. At doses near to the i.v. ED50 values for the antitussive activity, morphine (1.5mg kg- ', i.v.) and codeine (10mg kg-', i.v.) caused small but significant depressions of ventilation (7.0 +/- 2.3% and 16.5 +/- 8.4% respectively). Higher doses of morphine (10, 30 and 60mg kg- ', i.v.) caused further doserelated depression of ventilation (9.6 +/- 5.3%, 22.4 +/- 6.2% and 36.2 +/- 9.6% respectively) whereas codeine (30 and 60mg kg-' i.v.) caused stimulation of ventilation which was marked (191.3 +/- 43.9%) at 60 mg kg-'. 5. Compound BW443C in doses of 1 or 10mgkg-',i.v. (approximately equal to, and 10 times the EDo for antitussive activity) did not cause significant depression of ventilation. Only at higher doses of 30 and 60mg kg-', i.v. was there a significant decrease in minute volume (13.1 +/- 6.8% and 15.9 +/- 1.89% respectively). The depression of ventilation caused by either BW443C (60mg kg-', i.v.) or morphine (60mg kg-', i.v.) was prevented by pretreatment with naloxone (3mg kg-', i.v.) administered 15 min before morphine or BW443C. 6. These results in the guinea-pig support the hypothesis that the antitussive action of the opiates codeine and morphine and the opioid pentapeptide BW443C do not require penetration of these drugs into the CNS.
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PMID:Effects of codeine, morphine and a novel opioid pentapeptide BW443C, on cough, nociception and ventilation in the unanaesthetized guinea-pig. 334 36

1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bronchovascular dilatation induced by non-adrenergic, non-cholinergic (NANC) mechanisms observed in the dog exist in sheep. 2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prior thoracotomy. 3. Cumulative and factorial analysis of responses to randomized combinations of autonomic alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%. 4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separate alpha- and beta-adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator alpha-/beta-adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep. 5. Nitric oxide (NO) synthase inhibition in sheep using NG-nitro-L-arginine following blockade of alpha- and beta-adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects. 6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C-fibre axon reflex using substance P, calcitonin gene-related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects.
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PMID:Autonomic control of bronchial circulation in awake sheep during rest and behaviour. 940 60

1. Bradykinin (BK) is a nine amino acid peptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) formed from the plasma precursor kininogen during inflammation and tissue injury. The actions of BK are mediated by G protein-coupled cell surface receptors, designated B1 and B2. 2. BK has a plethora of effects in the airways including bronchoconstriction, bronchodilation, stimulation of cholinergic and sensory nerves, mucus secretion, cough and oedema resulting from promotion of microvascular leakage. These airway effects are mediated in the main by the B2 receptor subtype. 3. BK acts mainly indirectly, primarily through airway nerve activation, but also by the release of prostanoids, thromboxanes and nitric oxide (NO). 4. Airway responses to BK have been studied in detail in guinea-pigs, mice, sheep and rats. This review describes the effects of BK in these species and draws comparison with its effects in normal humans and patients with respiratory diseases. 5. Despite its many and varied effects in the airways of animals and man, the exact contribution of BK to airways disease remains unclear.
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PMID:Species differences in bradykinin receptor-mediated responses of the airways. 1242 22

Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO production, would improve the clinical outcome of TB by increasing NO production. In a randomised double-blind study, patients with smear-positive TB (n = 120) were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. Primary outcomes were sputum conversion, weight gain, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor-a. Compared with the human immunodeficiency virus (HIV)-/TB+ placebo group, the HIV-/TB+ patients in the arginine group showed significant improvement, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV-/TB+ arginine group (100.2 microM (range 90.5-109.9) versus 142.1 microM (range 114.1-170.1)) compared with the HIV-/TB+ placebo group (105.5 microM (range 93.7-117.3) versus 95.7 microM (range 82.4-108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo. Arginine is beneficial as an adjuvant treatment in human immunodeficiency virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide.
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PMID:Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis. 1266 6

Studies of angiotensin-converting enzyme inhibitor-induced cough have involved extensive use of experimental models in which guinea pigs are exposed to an inhaled stimulus such as capsaicin or citric acid. In the present study, we examined enalapril-induced potentiation of spontaneous cough in guinea pigs, without an inhaled stimulus. Daily oral administration of enalapril (3 mg/kg) for 20 to 30 days enhanced spontaneous cough. This enhancement of cough was inhibited by the bradykinin B(1) receptor antagonist des-Arg(10)-[Leu(9)]kallidin, but not by the bradykinin B(2) receptor antagonist icatibant. The amount of the bradykinin B(1) receptor agonist [3H]des-Arg(10)-kallidin specifically bound to membrane fractions from the trachea and larynx was increased by prolongation of the enalapril treatment, and positively correlated well with coughing frequency. In conclusion, the present results indicate that enalapril-induced cough is mediated by up-regulation of bradykinin B(1) receptors.
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PMID:Augmentation of spontaneous cough by enalapril through up-regulation of bradykinin B1 receptors in guinea pigs. 1292 71

1. Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Our previous results suggest that microvascular leakage induced, in the guinea-pig airways, by intra-oesophageal hydrochloric acid (HCl) infusion was mainly dependent on the release of tachykinins. Nociceptin, an endogenous ligand of the opioid receptor NOP, has been shown to inhibit bronchoconstriction and cough in guinea-pig or cat by inhibiting tachykinin release. 2. The purpose of this study was to investigate the effects of nociceptin on the intra-oesophageal HCl-induced airway microvascular leakage evaluated by Evans blue dye extravasation measurement in anaesthetised guinea-pigs pretreated with propranolol, atropine and phosphoramidon. 3. Infusion of intra-oesophageal HCl led to a significant increase in plasma extravasation in the main bronchi and trachea. This increase was abolished when animals underwent a bilateral vagotomy. 4. Airway microvascular leakage was inhibited by nociceptin (3-30 microg x kg(-1) i.v.) in a dose-dependent manner (maximal inhibition at the dose of 30 microg x kg(-1): 19.76+/-1.13 vs 90.92+/-14.00 ng x mg(-1) tissue for nociceptin and HCl infusion, respectively, in the main bronchi, P<0.01). The NOP receptor agonist [Arg(14),Lys(15)]N/OFQ mimicked the inhibitory effect of nociceptin, but at a 10-fold lower dose (3 microg x kg(-1) i.v). The NOP receptor antagonist J-113397 had no effect on plasma protein extravasation by itself, but was able to block the inhibitory effect of nociceptin. 5. Morphine (1 mg x kg(-1)) had a similar inhibitory effect as that of nociceptin. Naloxone pretreatment abolished the effect of morphine, but was enable to block the inhibitory effect of nociceptin. 6. Under similar conditions, nociceptin, in the previous range of concentration, was unable to counteract the airway microvascular leakage induced by substance P (SP). 7. These results suggest that airway plasma extravasation induced by intra-oesophageal HCl instillation might be inhibited by specific stimulation of the NOP receptor with nociceptin. Nociceptin is likely to act at a pre-junctional level, by inhibiting tachykinin release, since it was unable to prevent SP-induced airway plasma extravasation.
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PMID:Nociceptin inhibits airway microvascular leakage induced by HCl intra-oesophageal instillation. 1499 1

N-alpha-Tosyl l-arginine methyl ester [TAME]-esterase appears to be an important biochemical marker, which displays potent contractile properties on bronchial tissues and aorta in vitro. TAME-esterase induced contractions have been shown to be mediated via a nitric oxide-cyclic GMP pathway. TAME-esterase has also been described to be a possible new cardiovascular risk factor among smokers. TAME-esterase has been reported to be an enzyme, which is involved during the sequence of events leading to the activation of the kinin-kallikrein system. Use of aprotinin (a kallikrein inhibitor) as well as aspirin and indomethacin (prostaglandin inhibitors) have shown that there is an inter-dependent relationship between the kinin-kallikrein system and the cyclo-oxygenase pathway involved during the sequence of reactions leading to TAME-esterase induced contractions. Our findings also lend support to the concept of calcium antagonism whereby verapamil, and nifedipine, mimicked in reversible fashion the effects of Ca2+ withdrawal on muscle excitability during TAME-esterase induced contractions on rat aorta in vitro. We concluded that the effects of captopril, an ACE inhibitor, on TAME-esterase induced contractions could thus be due to the degradation of bradykinin by the enzyme kininase being blocked. This paper proposes an integrated model of possible biochemical-pharmacological pathways, which involve events leading to TAME-esterase induced contractions. We hypothesize that TAME-esterase induced cough through sensitization of airway sensor nerves in hypertensive patients taking angiotensin-converting enzyme inhibitors can be inhibited by aprotinin.
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PMID:Aprotinin suppresses ACE-inhibitor cough triggered by TAME-esterase. 1532 12

The advance of functional genomics revealed the superfamily of G-protein coupled receptors (GPCRs). Hundreds of GPCRs have been cloned but many of them are orphan GPCRs with unidentified ligands. The first identified orphan GPCR is the opioid receptor like orphan receptor, ORL1. It was cloned in 1994 during the identification of opioid receptor subtypes and was de-orphanized in 1995 by the discovery of its endogenous ligand, nociceptin or orphanin FQ (N/OFQ). This receptor was renamed as N/OFQ peptide (NOP) receptor. Several selective ligands acting at NOP receptors or other anti-N/OFQ agents have been reported. These include N/OFQ-derived peptides acting as agonists (cyclo[Cys(10),Cys(14)]N/OFQ, [Arg(14), Lys(15)]N/OFQ, [pX]Phe(4)N/OFQ(1-13)-NH(2), UFP-102, [(pF)Phe(4),Aib(7), Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)) or antagonists (Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)-NH(2), [Nphe(1)]N/OFQ(1-13)-NH(2), UFP-101, [Nphe(1), (pF)Phe(4),Aib(7),Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)), hexapeptides, other peptide derivatives (peptide III-BTD, ZP-120, OS-461, OS-462, OS-500), non-peptide agonists (NNC 63-0532, Ro 64-6198, (+)-5a compound, W-212393, 3-(4-piperidinyl)indoles, 3-(4-piperidinyl) pyrrolo[2,3-b]pyridines) and antagonists (TRK-820, J-113397, JTC-801, octahydrobenzimidazol-2-ones, 2-(1,2,4-oxadiazol-5-yl)-1 H-indole, N-benzyl-D-prolines, SB-612111), biostable RNA Spiegelmers specific against N/OFQ, and a functional antagonist, nocistatin. Buprenorphine and naloxone benzoylhydrazone are two opioid receptor ligands showing high affinity for NOP receptors. NOP receptor agonists might be beneficial in the treatment of pain, anxiety, stress-induced anorexia, cough, neurogenic bladder, edema, drug dependence, and, less promising, in cerebral ischemia and epilepsy, while antagonists might be of help in the management of pain, depression, dementia and Parkinsonism. N/OFQ is also involved in cardiovascular, gastrointestinal and immune regulation. Altered plasma levels of N/OFQ have been reported in patients with various pain states, depression and liver diseases. This review summarizes the pharmacological characteristics of, and studies with, the available NOP receptor ligands and their possible clinical implications.
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PMID:Nociceptin/orphanin FQ peptide receptors: pharmacology and clinical implications. 1726 36

Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in cirrhotic patients with moderate or severe malnutrition. PN should be started immediately when sufficientl oral or enteral feeding is not possible. ASH and cirrhosis patients who can be sufficiently fed either orally or enterally, but who have to abstain from food over a period of more than 12 hours (including nocturnal fasting) should receive basal glucose infusion (2-3 g/kg/d). Total PN is required if such fasting periods last longer than 72 h. PN in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV degrees with malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic patients or patients after liver transplantation should receive early postoperative PN after surgery if they cannot be sufficiently rally or enterally nourished. No recommendation can be made on donor or organ conditioning by parenteral administration of glutamine and arginine, aiming at minimising ischemia/reperfusion damage. In acute liver failure artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral nutrition should be administered via a nasoduodenal feeding tube.
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PMID:Hepatology - Guidelines on Parenteral Nutrition, Chapter 16. 2004 84

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