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In this report, we describe the ability of selective inhibitors of phosphodiesterase (PDE) isozymes to increase aminopyrine accumulation in rabbit isolated gastric glands. Aminopyrine accumulation in the presence of histamine was increased by the nonselective PDE inhibitor isobutylmethylxanthine (EC50 = 4.8 microM) and by two selective PDE IV inhibitors,(More)
BACKGROUND Ozone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We have shown previously that SP-D plays a protective role in a mouse model of allergic airway inflammation. Here we studied the role and(More)
The dog saphenous vein has postsynaptic subpopulations of both alpha-1 and alpha-2 adrenoceptors which are easily demonstrable using selective agonists and antagonists. Specific alpha-1 (methoxamine and SK&F 89748) or mixed alpha-1, alpha-2 (l-norepinephrine and M7) agonists as well as the specific alpha-2 agonist, BHT 920, cause concentration-related(More)
Addition of 5-HT or SK&F 103829 (2,3,4,5 tetrahydro-8[methyl-sulfonyl]-1 H-3-benzazepin-7-ol hydrobromide) contracts isolated strips of canine lower esophageal sphincter (LES) circular smooth muscle. 5-HT acts directly on the smooth muscle, since pretreatment with the neurotoxin TTX does not inhibit this contraction. Depletion of extracellular calcium or(More)
First-generation phosphodiesterase 4 (PDE4) inhibitors, such as rolipram, inhibit the activation of immune and inflammatory cells. The clinical use of these compounds is limited by gastrointestinal side effects, such as increased acid secretion and nausea. Consequently, the challenge has been to design novel PDE4 inhibitors that maintain the(More)
Electrical field stimulation (EFS) of isolated strips of opossum lower esophageal sphincter (LES) produced a relaxation that was accompanied by an elevation of intracellular cyclic GMP content. In order to compare the time dependence of the EFS-induced relaxation with that of the elevation of cyclic GMP, the ability of EFS to produce relaxation and increase(More)
1. Of the four major phosphodiesterase 4 (PDE4) subtypes, PDE4A, PDE4B and PDE4D are widely expressed in human inflammatory cells, including monocytes and T lymphocytes. We explored the functional role of these subtypes using ten subtype-selective PDE4 inhibitors, each belonging to one of two classes: (i) dual PDE4A/PDE4B inhibitors or (ii) PDE4D(More)
Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this(More)
Increases in cyclic adenosine monophosphate and cyclic guanosine monophosphate content accompany relaxation of isolated strips of opossum and canine lower oesophageal sphincter muscle. The aim of this investigation was to characterise these responses in isolated muscle from the human lower oesophageal sphincter. Electrical stimulation of enteric neurons(More)
The ability of the second generation phosphodiesterase 4 inhibitor SB 207499 (Ariflo), [c-4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)-r-l-cyclohexane carboxylic acid], to inhibit inflammatory cytokine production in vivo was evaluated and compared to that of rolipram, a first generation phosphodiesterase 4 inhibitor. To examine human tumor necrosis factor(More)