Pulmonary effects of type V cyclic GMP specific phosphodiesterase inhibition in the anaesthetized guinea‐pig

Turner, Nicholas C.; Dolan, John S.; Grimsditch, David C.; Lamb, Janine; Worby, Angela; Murray, Kenneth; Coates, William J.; Warrington, Brian H.

doi:10.1111/j.1476-5381.1994.tb14872.x

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…Mackay GA et al, where the role of cGMP in the functional modulation of mast cells and basophils was investigated, the potential of cGMP to caused potent inhibition of histamine release from rat peritoneal mast cells.The bronchodilatory potential of PDE5 inhibitor has been demonstrated in anaesthetized ventilated guineapigs where there was an inhibition of the histamine induced bronchoconstriction. Elevation in the cGMP levels in anaesthetized guinea-pig trachea was also seen[24]. In a guinea pig model of airway hyperresponsiveness tadalafil reduced specific airway resistance after nebulization of histamine, these results agree with ours.…”

supporting

confidence: 90%

A Case of Hepatitis A Virus Detection in River Water Flowing into Tidal Flats

Lee¹,

Cho²,

Chae³

et al. 2021

Int J Plant Anim Environ Sci

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Background: Cyclic nucleotides (cAMP and cGMP) act as secondary messengers in various cellular processes like signal transduction and inflammation. Sildenafil and tadalafil are phosphodiesterases-5 (PDE-5) inhibitors which prevent the degradation of these cyclic nucleotides and thus play a key role in regulating allergy, inflammation, and smooth muscle relaxation. The present study was conducted to ascertain the anti-allergic potential of Phosphodiesterase-5 inhibitors, sildenafil and tadalafil. Their effects on mast cell degranulation in animal model of bronchial asthma was explored.Method: An allergic model of bronchial asthma was developed. Wistar rats were first sensitized with 10 mg intraperitoneal (ip) ovalbumin adsorbed to 10 µg of aluminum hydroxide on day 0 and were subsequently divided into six groups (n=6). Animals

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supporting

confidence: 90%

A Case of Hepatitis A Virus Detection in River Water Flowing into Tidal Flats

Lee¹,

Cho²,

Chae³

et al. 2021

Int J Plant Anim Environ Sci

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“…The ¢nding, for the ¢rst time, that correction of the CFTR mucin secretion defect can be achieved by a selective PDE5 inhibitor is likely to have major impact for CF therapy. Thus, in view of its e¤cacy as a weak bronchodilator [27], its speci¢city, in that it does not increase cyclic AMP and it being one of a class of PDE5 inhibitors which includes Viagra0, this would provide a relatively safe compound in the development of a selective pharmacological therapy for cystic ¢brosis targeted at the gene protein defect.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of action of IBMX in correcting defective CFTR function was investigated using selective PDE3 (SB 95654) [26], PDE4 (rolipram, SB 95952) and PDE5 (SB96231) [27] inhibitors. Their structures are shown in Fig.…”

Section: Structure Of Selective Cyclic Nucleotide Pde Inhibitorsmentioning

confidence: 99%

A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein

et al. 1999

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A selective cyclic nucleotide PDE5 inhibitor corrected the defective mucin secretion response to the L L-agonist isoproterenol in submandibular acinar cells inhibited by antibody directed against the cystic fibrosis transmembrane conductance regulator. The PDE5 inhibitor was as effective as cpt-cyclic AMP or a selective PDE4 inhibitor. However, the PDE5 inhibitor had no effect on basal or isoproterenol-stimulated cyclic AMP levels and did not stimulate mucin secretion. The results showing, for the first time, correction of the CFTR mucin secretion defect by a PDE5 inhibitor, which may involve cyclic GMP, will have a major impact in development of a rational drug treatment for cystic fibrosis.z 1999 Federation of European Biochemical Societies.

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“…PDE3, PDE4 and mixed PDE3-4 inhibitors have been extensively studied for their effects on airway responsiveness and airway inflam-matory process [11−13], but few informations are available on the role of PDE5. PDE5 hydrolyses GMP, and inhibition of this isoenzyme induces a rise in cGMP content [14−16] which correlate with guinea-pig isolated trachea relaxation in vitro and the inhibition of histamineinduced bronchoconstriction in vivo, as suggested by an experiment using SK&F 96231, a selective PDE5 inhibitor [17,18]. However the functional role of PDE5 on airway tissues is still questionable as other PDE5 inhibitors, such as Zaprinast could not demonstrate potent bronchodilatory activities [17,19].…”

Section: Introductionmentioning

confidence: 99%

Experimental Studies on Guanosine 3’,5’-Cyclic Monophosphate Levels and Airway Responsiveness of the Novel Phosphodiesterase Type 5 Inhibitor

Kapui¹,

Schaeffer²,

Eg³

et al. 2011

Arzneimittelforschung

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The effect of 1-cyclopentyl-3-ethyl-6-(3-ethoxypyrid-4-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-one (SR 265579), a potent inhibitor of guanosine 3',5'-cyclic monophosphate (cyclic GMP) phosphodiesterase (PDE5), was examined regarding its specificity toward the other cyclic nucleotide phosphodiesterases, the effect on cyclic nucleotide levels and the bronchodilatory activity, both in vitro and in vivo in guinea-pigs. The effects were compared to those obtained with zaprinast (CAS 37762-06-4), a known PDE5 inhibitor. Anion-exchange chromatography of the soluble fraction of guinea-pig homogenates revealed 5 peaks which corresponded to PDE1, PDE2, PDE3, PDE4 and PDE5. SR 265579 produced a potent and competitive inhibition, with respect to cyclic GMP, of PDE5 with a Ki of 6.4 nmol/l. The compound was 25 fold more potent than zaprinast and demonstrated selectivity toward PDE5. The selectivity index was 14 and 33 with respect to PDE4 and 3, respectively. PDE1 and 2 were only inhibited at considerably higher concentrations. SR 265579 specifically increased the intracellular cyclic GMP levels in guinea-pig tracheal epithelial cells (EC 50 = 117 nmol/l). Moreover, in the guinea pig, plasma cyclic GMP levels were significantly increased after the intravenous or oral administration of doses as low as 1 mg/kg. Isolated guinea-pig trachea were relaxed by the addition of SR 265579 as evaluated by measuring either spontaneous tone or relaxation of histamine and acetylcholine-precontracted preparations. PD 2 values were of 7.64, 6.52 and 5.25, respectively. In vivo, after i.v. administration, bronchodilatory activity was demonstrated in an artificially-ventilated guinea-pig histamine-induced bronchospasm model with an ED 50 of 0.63 mg/ kg. In all experiments, SR-265579 was proved to be more active than zaprinast. These results demonstrate that SR 265579 is an orally active, potent and specific inhibitor of PDE5.

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Pulmonary effects of type V cyclic GMP specific phosphodiesterase inhibition in the anaesthetized guinea‐pig

Cited by 6 publications

References 14 publications

A Case of Hepatitis A Virus Detection in River Water Flowing into Tidal Flats

A Case of Hepatitis A Virus Detection in River Water Flowing into Tidal Flats

A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein

Experimental Studies on Guanosine 3’,5’-Cyclic Monophosphate Levels and Airway Responsiveness of the Novel Phosphodiesterase Type 5 Inhibitor

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