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)

Effects of selective mu and delta receptor agonists on capsaicin-induced cough reflex in rats were studied. Intracisternal injection (i.cist.) of a selective mu receptor agonist [D-Ala2,Mephe4,Gly-ol5]enkephalin (DAMGO) produced dose-related depression of coughs over the 0.003-0.03 nmol dose range. The antitussive potency of DAMGO was 100-fold more potent than morphine. The antitussive effects of DAMGO and morphine were significantly reduced by naloxone (1 nmol i.cist.). The selective delta receptor agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE), at a dose of 10 nmol (i.cist.), had no significant effect on the number of coughs. When co-administered i.cist., DPDPE (10 nmol) consistently and significantly decreased the antitussive potencies of DAMGO and morphine. The decrease in the antitussive effects of DAMGO and morphine caused by DPDPE were prevented by selective delta receptor antagonist, naltrindole (3 nmol). These results suggest that the antitussive effects of opioids are mediated predominantly by mu receptors, and delta receptors may play an inhibitory role in antitussive processes that are mediated by the mu receptors.
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PMID:Modulation of mu-mediated antitussive activity in rats by a delta agonist. 166 89

The pharmacological actions of double-enkephalin (biphalin; (HCl-Try-D-Ala-Gly-Phe-NH-)2) an analogue of enkephalin, on nociception, respiration and the cough reflex were compared with those of morphine in anesthetized rats. Double-enkephalin (D-Enk), injected i.p., produced significant analgesia at doses of 10 and 20 mg/kg in a hot-plate test. The analgesic effect of D-Enk was antagonized by pretreatment with naloxone (5 mg/kg, i.p.). D-Enk and morphine (M) produced a dose-dependent decrease in the frequency of respiration (RF) and in the tidal volume (Vt). However, the effects of D-Enk on RF and Vt were significantly weaker than those of M. The 50% antitussive dose (AtD50) of D-Enk and M were 0.63 and 0.48 mg/kg, i.p., respectively. The antitussive effect of D-Enk was antagonized by pretreatment with naloxone (0.4 mg/kg, i.p.). These results suggest that D-Enk exerted an antitussive effect similar to that of morphine, and that the involvement of opiate receptors is associated with the antitussive effect of D-Enk.
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PMID:Effects of double-enkephalin (biphalin), an enkephalin analogue, on respiration and the cough reflex in rats. 321 86

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

The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so-called 'atopy gene' in 11q13 is not linked to atopy but is associated with serum IgE levels. The beta2-adrenergic receptor gene on 5q32-33 was found to have polymorphism by Ban I and to be related to beta2-receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to beta2-agonists. This defect is also related to higher prevalence on non-atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of beta2-receptors was lower and Gln27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.
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PMID:Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor-induced cough. 965 60

We studied the central and peripheral antitussive effect of ORL(1) receptor activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 microg) given directly into the CNS by an intracerebroventricular (i.c.v.) route inhibited cough elicited by capsaicin exposure by approximately 23, 29 and 52%, respectively. The antitussive activity of nociceptin/orphanin FQ (90 microg, i.c.v.) was blocked by the selective ORL(1) antagonist [Phe(1)gamma(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) (180 microg, i.c.v.) and J113397 (10 mg kg(-1), i.p.) but not by the opioid antagonist, naltrexone (3 mg kg(-1), i.p.). Furthermore, intravenous (i.v.) nociceptin/orphanin FQ (1.0 and 3.0 mg kg(-1)) also inhibited cough approximately by 25 and 42%, respectively. These findings indicate that selective ORL(1) agonists display the potential to inhibit cough by both a central and peripheral mechanism, and potentially represent a novel therapeutic approach for the treatment of cough.
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PMID:Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors. 1125 Aug 66

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

We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (Tt). At the higher concentrations (5 mM and 1 mM, respectively), both drugs abolished the cough reflex. DAMGO and baclofen also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased Tt, owing to increases in expiratory time. The neurokinin-1 (NK(1)) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK(2) receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.
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PMID:Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit. 2065 Dec 22

We report the case of a boy with a history of atopic dermatitis starting in infancy. At the age of four, his family moved into a newly built house at the foot of a mountain. One year later, he was diagnosed with Japanese Cedar pollinosis. During the same year, in March, he began to experience oral symptoms, hoarseness, and coughing, after eating multiple types of fruits and vegetables, like soybeans, apples, etc. His tests for Bet v1 and the pathogenesis-related protein-10 (PR-10) of the corresponding foods were positive; accordingly, he was diagnosed with Pollen Food Allergy Syndrome (PFAS). In order to investigate the relationship between pollen and food allergies, we counted the pollen grains dispersed at the patient's house during a period of one year and measured his specific IgE titers for pollen and food allergens every three months. We found a large amount of Japanese cedar, cypress, oak, and various other species of pollen dispersed at the patient's house. All counts were higher than the average pollen counts in the city of Fukuoka. After the seasonal dispersal of oak pollen, the patient's specific IgE antibody titers against Alder, Oak, Bet v1, Gly m4, and PR-10 protein group of fruits increased, although alder pollen was not detected. We thus inferred that the patient had developed PFAS by exposure to a large amount of Fagales species pollen, including oak.
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PMID:[POLLEN FOOD ALLERGY SYNDROME IN A FIVE-YEAR-OLD BOY AFTER MOVING HOUSE AT THE FOOT OF THE MOUNTAIN: A CASE REPORT]. 3024 52