Search results for "c-AMP"

Cardiovascular effects induced by rolipram, a selective cAMP phosphodiesterase inhibitor: Interaction with adrenergic and calcium affecting drugs

1990

Traditional Chinese herbal medicine at the forefront battle against COVID-19: Clinical experience and scientific basis.

2020

Abstract Background Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics’ infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy. Approach We conducted conduct a systematic survey of various TCM herbal pre…

Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.

1993

1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human…

Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells

2005

Background: A common pathological feature of chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) is mucus hypersecretion. MUC5AC is the predominant mucin gene expressed in healthy airways and is increased in asthmatic and COPD patients. Recent clinical trials indicate that phosphodiesterase type 4 (PDE4) inhibitors may have therapeutic value for COPD and asthma. However, their direct effects on mucin expression have been scarcely investigated. Methods: MUC5AC mRNA and protein expression were examined in cultured human airway epithelial cells (A549) and in human isolated bronchial tissue stimulated with epidermal growth factor (EGF; 25 ng/ml).…

The phototransduction cascade in the isolated chick pineal gland revisited.

2003

It is well established that the isolated chick pineal gland is directly light sensitive and that melatonin synthesis of the gland can be inhibited by exposing the gland to light during scotophase. Since not all the steps of the phototransduction cascade have been clarified to the same extent as in the retina, we have treated isolated chick pineal glands with 90 min of light during scotophase and with drugs that affect key-components of vertebrate phototransduction, i.e., cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6), cGMP levels and cGMP-gated calcium channels. The endpoint measured was the activity of the rate-limiting enzyme of melatonin synthesis, arylalkylamine N-acet…

β-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E 2 -inhibitory effects in human neutrophils

2000

Human neutrophils were treated for 4 h with a combination of salbutamol (1 µM), a β2-adrenoceptor agonist, and rolipram (30 µM), a selective phosphodiesterase 4 inhibitor, to investigate whether this treatment produces up-regulation of phosphodiesterase activity with functional consequences. Anion-exchange chromatography coupled with the use of selective activators and inhibitors demonstrated that a phosphodiesterase activity with characteristics of the isoenzyme type 4 was increased in drug-treated cells. Kinetic analysis showed a ~1.5-fold increase in V max without alteration of K m values. The augmented phosphodiesterase activity in drug-treated cells was abolished by actinomycin D. Cycl…

PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression.

2004

Phosphodiesterase 4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have demonstrated a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The initially detected side effects, mainly nausea and emesis, appear at least pa…

Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils.

2000

Objective: To investigate whether histamine produces up-regulation of phosphodiesterase (PDE) activity with functional consequences in human peripheral blood neutrophils.¶Methods: PDE activity was studied by a radioisotopic method following anion-exchange chromatography. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of mRNA transcripts of PDE4 subtypes. Cyclic AMP (cAMP) levels were measured by enzyme-immunoassay, and superoxide generation by cytochrome c reduction.¶Treatment: Neutrophils were incubated for 4 h with histamine (1 μM).¶Results: PDE4 was the only isoenzyme activity increased in treated neutrophils. Kinetic analysis showed a ∼1.5-fold increase …

Effects of inhaled glaucine on pulmonary responses to antigen in sensitized guinea pigs.

2000

The alkaloid (S)-(+)-1,2,9,10-tetramethoxyaporphine (glaucine) is a phosphodiesterase 4 inhibitor with bronchodilator and anti-inflammatory activity in vitro. In this study, we examined the in vivo effects of glaucine on an animal model of asthma. In ovalbumin sensitized guinea pigs, inhaled glaucine (10 mg ml(-1), 3 min) inhibited the acute bronchoconstriction produced by aerosol antigen (antigen response was 256+/-42 and 95+/-14 cm H(2)O l(-1) s(-1) in control and glaucine-treated animals, respectively; P<0.05). Pretreatment with glaucine (10 mg ml(-1), 10 min inhalation, 30 min pre- and 3 h post-antigen exposure) markedly reduced airway hyperreactivity to histamine, eosinophil lung accum…

Multiple actions of glaucine on cyclic nucleotide phosphodiesterases, α1-adrenoceptor and benzothiazepine binding site at the calcium channel

1992

1. In the present study, the properties of glaucine (an aporphine structurally related to papaverine) were compared with those of papaverine, diltiazem, nifedipine and prazosin. The work includes functional studies on rat isolated aorta contracted with noradrenaline, caffeine or KCl, and a determination of the affinity of glaucine at calcium channel binding sites of alpha-adrenoceptors, by use of [3H]-(+)-cis-diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The effects of glaucine on the different molecular forms of cyclic nucleotide phosphodiesterases (PDE) isolated from bovine aorta were also determined. 2. Contraction evoked by noradrenaline (1 micro…