Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cecropia pachystachya Mart. is popularly called "ambay" and extensively used in herbal medicine of South America for cough and asthma. In Argentina it grows in neotropical rainforest (Ntr C.p.) and in a temperate region (Tp C.p.). In a previous work we showed their hypotensive properties with different potency and toxicity, and now we studied the Tp C.p. effects in isolated heart from rats and central effects of both plants on the open-field test for mice. Tp C.p. produced a positive inotropic effect on isolated rat hearts, which was not affected by 1 microM propranolol, suggesting that it is not due to a beta-adrenergic effect. In contrast, it was prevented by pretreatment with high [K](o) media, which stimulates the Na,K-ATPase pump, suggesting an inhibition of the pump by "ambay", as digital do. In the open-field test, both Ntr C.p. and Tp C.p. similarly decreased the spontaneous locomotion and exploratory behavior of mice at doses between 180 and 600 mg/kg. Ntr C.p. potentiated the effect of 3 mg/kg diazepam to one similar to 10 mg/kg diazepam, but was not antagonized by 0.5 mg/kg flumazenil. Amphetamine at 5 mg/kg prevented the sedative effect of Ntr C.p. Chromatographic analysis showed that both plants have a qualitatively similar fingerprint but quantitatively differed in at least three components. Although the purpose was not to identify them, both plants have at least 10 compounds. Two of them were in higher amount in Tp C.p. than in Ntr C.p., and then, they could be responsible for the cardiovascular toxicity of Tp C.p. In conclusion, the results suggest that ambay has cardiotonic and sedative properties. The sedative effect could be useful in cough treatment. The extract resulted additive to benzodiazepines but it did not bind to the same site on GABA-A receptor, and it was interfered by the dopamine release produced with amphetamine.
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PMID:Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice. 1641 16

One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease. However, even in health, the ASL is slightly acidic, and this acidity might be part of normal airway defense. Only recently research has focused on the mechanisms responsible for acid and base secretion into the ASL. Advances resulted from research into the airway disease associated with cystic fibrosis (CF) after it was found that the CFTR Cl(-) channel conducts HCO (3) (-) and, therefore, may contribute to ASL pH. However, the acidity of the ASL indicated parallel mechanisms for H(+) secretion. Recent investigations identified several H(+) transporters in the apical membrane of the airway epithelium. These include H(+) channels and ATP-driven H(+) pumps, including a non-gastric isoform of the H(+)-K(+) ATPase and a vacuolar-type H(+) ATPase. Current knowledge of acid and base transporters and their potential roles in airway mucosal pH regulation is reviewed here.
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PMID:Mechanisms of acid and base secretion by the airway epithelium. 1709 Dec 14

We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na(+)-K(+) ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the alpha(3) subunit of Na(+)-K(+) ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitability in vitro, and coughing in vivo are potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation.
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PMID:Selective expression of a sodium pump isozyme by cough receptors and evidence for its essential role in regulating cough. 1986 78

Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed on airway nerve fibers that modulates afferent signals, resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+-ATPase-2. In guinea pig tracheal ring organ bath experiments, the TRPV1 agonist capsaicin led to ASM contraction, but this contraction was significantly attenuated by the sodium channel inhibitor bupivacaine (n = 4, P < 0.05) and the neurokinin-2 receptor antagonist GR-159897 (n = 4, P < 0.05), suggesting that this contraction is neutrally mediated. However, pretreatment of guinea pig and human ASM in organ bath experiments with the TRPV1 antagonist capsazepine inhibited the maintenance phase of an acetylcholine-induced contraction (n = 4, P < 0.01 for both species). Similarly, capsazepine inhibited methacholine-induced contraction of peripheral airways in mouse precision-cut lung slice (PCLS) experiments (n = 4-5, P < 0.05). Although capsazepine did not inhibit store-operated calcium entry in mouse ASM cells in PCLS (n = 4-7, P = nonsignificant), it did inhibit calcium oscillations (n = 3, P < 0.001). These studies suggest that TRPV1 is expressed on ASM, including the SR, but that ASM TRPV1 activation does not play a significant role in initiation of ASM contraction. However, capsazepine does inhibit maintenance of contraction, likely by inhibiting calcium oscillations.
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PMID:Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling. 2833 10

Calcium is important for physiological functioning in many tissues and is essential in mucus secretion and muscle contraction. Intracellular concentrations of calcium are regulated by calcium-related proteins, such as transient receptor potential cation channel subfamily V member 4 (TRPV 4), TRPV6, Calbindin-D9k (CaBP-9k), sodium-calcium exchanger (NCX1), and plasma membrane Ca2+ ATPase 1 (PMCA1). In this study, the relationship between secretion of pulmonary mucus and calcium regulation was investigated. To confirm the effect of steroid hormones, immature mice were injected with estrogen (E2) or progesterone (P4), and mature mice were injected with dexamethasone (DEX). Subsequently, the location and expression of TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 in lung tissue were examined. Periodic acid-Schiff staining was performed to investigate functional aspects of the protein expression. There were no significant differences in calcium-related gene expression in E2- and P4-treated mice, but TRPV4, NCX1, and PMCA1 were increased in DEX-treated mice and were recovered by RU486 treatment. DEX induces the expression of calcium-related proteins through the glucocorticoid receptor-mediated pathway and may involve decreased mucin secretion in the bronchiole. TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 were specifically expressed in Clara and alveolar type 2 cells of mouse lung. CC10, a marker of Clara cells, was decreased by DEX. In addition, mucin secretion, which is a functional aspect of this cell, was also decreased by DEX treatment. Control of calcium-related gene expression may affect the control of mucus secretion in the lung. Such a control mechanism can form the basis of studies into diseases such as inflammation attributable to mucus secretion abnormalities, coughing, and respiratory disorders and distress.
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PMID:Inhibition of mucin secretion via glucocorticoid-induced regulation of calcium-related proteins in mouse lung. 2944 20