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)

The effects of orally ingested dihomo-gamma-linolenic acid (DHLA), the natural biosynthetic precursor of prostaglandin E1 (PGE1), were assessed in human volunteers. Single doses of DHLA (0.1--2g) increased the proportion of DHLA relative to arachidonic acid in plasma and platelets and also increased the ex-vivo capacity of platelets to produce PGE1 and PGE2. More pronounced effects were observed during sustained treatment (five days to four weeks) when DHLA also accumulated in red cell membranes. These biochemical changes were accompanied by potentially antithrombotic changes in haemostatic function. The most common effect, which was consistently detected after 0.1-g single doses of DHLA or its methyl ester, was a decrease in plasma heparin-neutralising activity. Inhibition of platelet aggregation induced by adenosine diphosphate was also detected, though this was generally less pronounced. Sustained treatment in one subject also produced definite inhibition of ristocetin-induced platelet aggregation. There was only one possible adverse effect--a transient cough in a subject with a history of asthma. DHLA therefore seems to have considerable potential as an agent for preventing and treating human thromboembolic disease.
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PMID:Antithrombotic potential of dihomo-gamma-linolenic acid in man. 33 12

Benazepril (CGS 14824A HCl) is a new prodrug type angiotensin converting enzyme (ACE) inhibitor. The active form is considered to be benazeprilat, a diacid hydrolyzed compound. Benazepril and benazeprilat inhibited the contraction induced by exposure with angiotensin I, not angiotensin II, in the isolated rabbit aorta. The ACE inhibiting activity of benazeprilat was 1000 times more potent than that of benazepril in this experiment. Benazepril as well as benazeprilat and captopril exerted little influence on norepinephrine, serotonin and high K(+)-induced contraction or bradykinin-induced relaxation in isolated blood vessel preparations, thus angiotensin II synthesis inhibition seemed to be the main cause for its vasodilation. Benazepril, unlike benazeprilat or captopril showed considerable influence on prostaglandin (PG)-induced responses at higher concentrations. The vasocontraction induced by PGF2 alpha was competitively antagonized at 10(-5)-10(-4) mol/l, while vascular responses induced by PGE1, PGE2 or PGI2 was inhibited at 3 x 10(-4) mol/l of benazepril. Although these influences on PGs might not contribute much to its vasodilatory mechanism, the action seemed interesting in relation to cough induction, a known side effect of ACE inhibitors in the market. Benazepril has two asymmetric carbon atoms, thus four optical isomers are possible, SS (benazepril), SR (CGP 14'829A), RS (CGP 42'454A), RR (CGP 42'456A). The SS configuration was the most potent for antagonizing angiotensin I-induced vasocontraction, which seemed to be the best fitted for the ACE molecule.
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PMID:Antihypertensive mechanism of action of the novel angiotensin converting enzyme inhibitor benazepril. Effect on isolated vascular preparations. 208 Sep 46

Cough is a well recognised though undesirable side effect during the course of treatment with angiotensin converting enzyme inhibitors (IEC). With the help of two examples we have tried to show that this cough does not have an immunological origin but rather pharmacological. Cough was suppressed by non steroidal anti-inflammatory drugs. Stemming from these observations and from two studies in the literature a patho-physiological mechanism for the cough is proposed in which treatment with IEC leads to a connection with prostaglandins, notably bronchial PGE2.
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PMID:[Cough provoked by angiotensin-converting enzyme inhibitors. Effect of non-steroidal anti-inflammatory agents]. 321 98

We evaluated in a double-blind study the bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1 (PGE1-carbinol), described recently as a nonirritant bronchodilator in animals. Fifteen asthmatic patients received by inhalation single doses of 1, 10, and 30 micrograms PGE1-carbinol, 55 micrograms PGE2, and placebo (10% ethanol in normal saline, which was also used as diluent for the PGs). Such pulmonary function tests as forced expiratory volume in 1 second, forced vital capacity, and maximal expiratory flow were monitored during 2 hours following inhalation of each compound. 10 and 30 micrograms PGE1-carbinol produced significant but short-acting bronchodilation, similar to that caused by 55 micrograms PGE2. One-third of the patients reported mild cough and throat irritation during and shortly after inhalation of 30 micrograms PGE1-carbinol or 55 micrograms PGE2. Placebo and 1 microgram PGE1-carbinol produced minimal side effects, but neither agent caused bronchodilation. In an adjunctive, unblinded trial, the same patients received 400 micrograms fenoterol. Fenoterol caused greater bronchodilation 15 and 30 minutes after inhalation than did the PGs in the double-blind study.
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PMID:Bronchodilatory properties of 2-decarboxy-2-hydroxymethyl prostaglandin E1. 385 12

The relative bronchomotor activities of prostaglandins (PG) E1, E2, F2 alpha, F2 beta and I2 and of three synthetic E prostaglandin analogues (TR4161, TR4367 and TR4752) were determined on a large number of isolated preparations of guinea-pig trachea and human bronchial muscle. Each prostaglandin was capable of eliciting both contraction and relaxation, the relative incidence of these responses partly depending on concentration. TR4161 was a virtually pure relaxant; TR4367 was virtually devoid of bronchomotor activity; and TR4752 was a potent relaxant, devoid of contractant activity. The results also provided distinct rank orders of approximate potency for contraction and relaxation. Tachyphylaxis to the relaxant activities of PGE1 and TR4752 confirmed the underlying contractant activity of the two natural E prostaglandins. Antagonism with a high dose of indomethacin of the contractant actions of PGE1, PGE2 and PGF2 alpha confirmed the presence of relaxant activities in each. Inhaled aerosols of the same natural and synthetic prostaglandins were evaluated for irritant activity on the airways, using the cough response of the restrained conscious cat. All of them, except TR4161, elicited severe coughing. The rank order of potencies for irritancy differed from those for tracheobronchial contractant and relaxant activities. These findings suggest that the three responses studied arise from the activation of three distinct PG receptors in the airways. We propose the terms chi (contractant), psi (relaxant) and omega (irritant) for these putative receptors for prostaglandins or possibly other prostanoids.
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PMID:Specific receptors for prostaglandins in airways. 624 49

Prostaglandin D2 (PGD2) and some naturally occurring and synthetic prostaglandin (PG) analogues were evaluated for irritant/ tussive activity in cats. PGD2, PGF2 alpha and ICI81008 were potent tussive agents when inhaled, producing both an early and late phase of coughing. In addition all three prostaglandins decreased respiratory rate. In contrast PGE2, PGE1 and PGA1 were 100-1000 times less potent than PGF2 alpha as irritants and weakly stimulated respiratory rate. The PGE class of compounds only produced an early phase of coughing. The rank order of early phase tussive activity was ICI81008 greater than PGF2 alpha greater than PGF2 beta much greater than PGE1 = PGE2 = PGA1. This rank order is similar to that characterising the prostanoid 'X' contractant or class II receptor(s).
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PMID:Tussive activity of inhaled PGD2 in the cat and characterisation of the receptor(s) involved. 632 41

1 Electrical and mechanical properties of smooth muscle cells or of neuro-effector transmission in the smooth muscle layer of the dog trachea, were studied after treatment with indomethacin, by means of the double sucrose gap, microelectrode or tension recording methods. 2 After several subcutaneous injections of indomethacin (1.0 mg/kg daily), 6 out of 12 dogs were coughing and wheezing. 3 Smooth muscle tissues dissected from the trachea of the coughing dog showed spontaneous electrical and mechanical activities at the frequency of 8-15 per min. These spontaneous electrical and mechanical activities were completely suppressed by treatment with atropine (10(-6) M), isoprenaline (5 X 10(-7) M) or prostaglandin E2 (10(-9) M) but not by tetrodotoxin (1.5 X 10(-6) M). 4 Direct muscle stimulation induced oscillatory potential changes followed by tension development in the trachea of the indomethacin-treated dog. 5 In the indomethacin-treated dog, mean membrane potential of the tracheal smooth muscle cells was -52.4 mV, and in the control trachea, the potential was -59.0 mV. 6 In the trachea from control dogs, the amplitude of test e.j.ps after conditioning e.j.ps was always smaller than the conditioning e.j.p., at any time interval between the two stimuli. In the trachea from indomethacin-treated dogs, facilitation phenomena were observed. 7 In the trachea from the indomethacin-treated dog, prostaglandin E1 (PGE1) or PGE2 (10(-10)-10(-9) M) markedly suppressed the amplitude of the e.j.p. but did not affect the facilitation phenomenon. 8 These results indicate that endogenous prostaglandins play important physiological roles in the feed-back inhibitory mechanisms for acetylcholine release from the nerve terminals during the resting and active states. 9 The results are also discussed in relation to the genesis of aspirin-induced asthma in man.
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PMID:Spontaneous activity in the trachea of dogs treated with indomethacin: an experimental model for aspirin-related asthma. 723 2

The proposal that some naturally occurring prostaglandins (PGs) or their by-products may be implicated in the pathogenesis of the asthmatic bronchospasm has been suggested. Other PGs may be potentially useful in the treatment of this lung disease. The present investigation compared the bronchodilator effects of PGE1 and PGE2 in pharmacologically constricted experimental animals. In pentobarbital-anesthetized, spontaneously breathing dogs, aerosols of PGE1 and PGE2, 0.0002 to 0.2%, effectively inhibited the increases in pulmonary resistance (RL) and decreases in dynamic lung compliance (CDYN) produced by PGF2 alpha (3.0 micrograms/kg i.v.). PGE2 was found to be more effective than PGE1 in preventing RL responses to PGF2 alpha; however, both bronchodilators were equally effective vs. CDYN changes. These agents inhibited central airway constriction more than peripheral. Transient decreases in systemic arterial pressure and increases in heart rate occurred especially at the higher concentrations. In a group of trained conscious dogs, effective concentrations did not evoke adverse subjective discomfort or irritation. Higher concentrations, i.e., 1.0%, did produce coughing, breathholding, restlessness and altered patterns of breathing. In normal or sensitized guinea pigs, PGE aerosols were effective in reducing the bronchopulmonary provocation produced by histamine or specific antigen. These in vivo results suggest that aerosols of the classical PGEs are effective bronchospasmolytics in laboratory animals and that irritation may be related to concentration.
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PMID:Inhibition of bronchoconstriction by aerosols of prostaglandins E1 and E2. 739 72

The aim of this study was to investigate if prostaglandin (PG) metabolism is altered by angiotensin-converting enzyme (ACE) inhibitors as determined in the broncho-alveolar lavage fluid (BALF) of the guinea pig. Enalapril or imidapril was orally administered once a day for 2 weeks to Hartley male guinea pigs. Twenty-four hours after the last treatment, BALF was collected and the concentrations of PGI2, thromboxane A2 (TXA2) and PGE2 were measured by enzyme immunoassay. Enalapril significanlty P < 0.05) increased the TXA2 content, which was inhibited by indomethacin treatment and significantly (P < 0.05) decreased the PGI2 content. Imidapril, however, did not affect TXA2 or PGI2 generation. These findings suggest that altered PG metabolism may be associated with coughing as a side effect of enalapril.
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PMID:Altered prostaglandin metabolism induced by angiotensin-converting enzyme inhibitors in broncho-alveolar lavage fluid of the guinea pig. 890 95

Bronchopulmonary C-fiber afferents are characterized by their distinct sensitivity to chemical stimuli in the airways or pulmonary circulation. Responses evoked by activating these afferents are mediated by both central reflex pathways and by local or axon reflexes involving the release of tachykinins from sensory endings. Bronchopulmonary C-fiber stimulation reflexly reduces tidal volume and increases respiratory rate, constricts the airways, increases mucus secretion in the airways, and is associated with coughing. Cardiovascular effects include bradycardia, a fall in cardiac output, and bronchial vasodilation that increases airway blood flow despite systemic hypotension. In animals, C-fiber stimulation inhibits skeletal muscle activity, and in humans, is accompanied by burning and choking sensations in the throat and upper chest. Recent studies have identified additional physiologic and pharmacologic stimuli to these afferents, such as hydrogen ions, adenosine, reactive oxygen species, and hyperosmotic solutions. Furthermore, increasing evidence indicates that the excitability of these afferents is enhanced by the local release of certain autocoids (e.g. PGE2) during airway inflammation. These findings further indicate that vagal C-fiber endings in the lungs and airways play an important role in regulating the cardiopulmonary functions under both normal and abnormal physiologic conditions.
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PMID:Afferent properties and reflex functions of bronchopulmonary C-fibers. 1124 Jan 52


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