Increased Levels of Free Serotonin in Plasma of Symptomatic Asthmatic Patients

Lechín, Fuad; Dijs, Bertha van der; Orozco, Beatriz; Lechin, Marcel E.; Lechin, Alex E.

doi:10.1016/s1081-1206(10)63263-2

Cited by 120 publications

(101 citation statements)

References 47 publications

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“…The DTD1 gene counters this process and interacts with tyrRS by possessing a d-tyrosyl-tRNA deacylase that cleaves the ester bond between a tRNA molecule and a d-amino acid (21). Misregulation of DTD1 gene expression may increase the toxicity of d-amino acids such as d-tryptophan, an enzyme that has been implicated in AIA etiology by producing kynurenine and serotonin (18)(19)(20). Furthermore, Wakasugi and Schimmel have revealed that cytoplasmic tyrRS has proinflammatory cytokine functions similar to interleukin-8 (IL-8) and to the endothelial monocyte-activating polypeptide II (EMAP II) (33).…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact molecular mechanisms are not clear, the DTD1 gene can counteract the accumulation of inactive tRNA molecules (14) and promote defense mechanisms against the harmful effects of d-amino acids including tryptophan, an enzyme that is down-regulated by aspirin (40) and has been implicated in AIA susceptibility in several studies (18)(19)(20). The small sample size (n=592) may serve as a potential limitation to this preliminary study, and therefore, in order to clarify the relationship between DTD1 variants and the risk of AIA with high statistical power, further replication studies should use larger scale samples in various ethnic groups (n>1,000).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…during the activation of cellular immune responses, interferon (IFN)-γ induces the enzyme indoleamine 2,3-dioxygenase (IdO), which catalyzes tryptophan into kynurenine and serotonin (15), resulting in inhibition of T-cell proliferation (16) and increased severity of allergic asthma (17). Elevated levels of serum kynurenine and serotonin in individuals with various degrees of chronic airway obstruction compared to non-asthmatic controls provide evidence that tryptophan may play a role in asthma pathogenesis (18)(19)(20). In particular, inactivation or misregulation of the DTD1 gene, may hamper the recycling of misacylated tRNA molecules and lead to an increase in the toxicity of d-amino acids including tryptophan (21).…”

Section: Introductionmentioning

confidence: 99%

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Association analysis of DTD1 gene variations with aspirin-intolerance in asthmatics

Pasaje

Bae²,

Park³

et al. 2011

Int J Mol Med

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Abstract. Aspirin ingestion is a common precipitating factor of life-threatening asthma attacks, requiring some patients to undergo mechanical ventilation. The gene, d-tyrosyl-tRNA deacylase 1 (DTD1), may be a risk factor for aspirin-intolerant asthma (AIA) by catalyzing the hydrolysis of d-tryptophan and interacting with the tyrosyl-tRNA synthetase (tyrRS) enzyme, which promotes a pro-inflammatory phenotype. In order to investigate the association of DTD1 variants with the risk of AIA in an asthma cohort, 38 single nucleotide polymorphisms (SNPs) were genotyped and 5 major haplotypes were obtained in 163 AIA cases and 429 aspirin-tolerant asthma (ATA) controls. differences in DTD1 SNP and haplotype distributions were analyzed using logistic and multiple regression models and were adjusted for age, gender, smoking status, atopy and body mass index (BMI) as covariates. Subsequent analyses revealed no association between DTD1 variants and the risk of AIA. Although nominal evidence of an association was detected between several DTD1 variants and the rate of decline of the forced expiratory volume in the first second (FEV 1 ) in AIA patients (rs6136444, rs6136469, rs6081338 and DTD1_ht5; P=0.01-0.02), the signals reached the threshold of multiple testing corrections, suggesting that DTD1 variants do not affect the abnormalities of the upper airways in AIA patients.

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Section: Discussionmentioning

confidence: 99%

Section: ------------------------------------------------------------mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association analysis of DTD1 gene variations with aspirin-intolerance in asthmatics

Pasaje

Bae²,

Park³

et al. 2011

Int J Mol Med

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“…CSA and bronchial asthma show similar clinical pathophysiologies and pathogeneses, such as disturbances of the parasympathetic nervous system, 16,17,49 increases in the endothelin, 50,51 thromboxane A2 52,53 and serotonin 54,55 levels, and involvement of inflammation. 56,57 However, the mechanisms of the linkage between the 2 diseases remain unknown.…”

Section: Circulation Journal Vol71 February 2007mentioning

confidence: 95%

Airway Hyperresponsiveness in Patients With Coronary Spastic Angina Relationship Between Coronary Spasticity and Airway Responsiveness

Shoji

Okayama²,

Uchida

et al. 2007

Circ J

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Background Several reports have suggested a possible link between bronchial asthma and coronary spasm, but the possibility of a relationship in coronary spastic angina (CSA) has not been clarified. Methods and ResultsAirway responsiveness to methacholine and coronary spasticity to acetylcholine were examined in 42 patients with CSA and 36 patients with chest pain syndrome (CP). Furthermore, 18 control subjects were examined and their airway responsiveness compared with that of the CSA and CP patients. The incidence of airway hyperresponsiveness was significantly higher in the CSA group (74%) than in the CP (19%) and control (17%) groups (p<0.0001). The geometric mean of the log minimum dose (Dmin), defined as the cumulative dose at the point at which respiratory conductance began to decrease, was significantly lower in the CSA group (0.75 log units) than in the CP (1.20 log units) and control (1.38 log units) groups (p=0.004). Conclusion These results demonstrate that acetylcholine-induced coronary spasticity is significantly related to methacholine-induced airway responsiveness in patients with CSA. A generalized hyperresponsiveness of the vascular and nonvascular smooth muscles, including that through cholinergic mechanisms, may exist in patients with CSA. (Circ J 2007; 71: 234 -241)

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“…In subjects with asthma, plasma levels of 5HT are elevated and correlate with clinical severity rating and FEV1 (23). One possible source of 5-HT are the endocrine cells of the lung (24); an increase in the number of endocrine cells (and presumably 5-HT) has been described in bronchiectatic lungs, lung containing neoplasms and lungs of subjects exposed to hypoxia (25).…”

mentioning

confidence: 99%

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD

Pauwels

Joos

Fogarty

et al. 2008

Pulmonary Pharmacology & Therapeutics

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The objectives of this study were to determine the effect of single and repeat dosing with oral ondansetron, a 5-HT3-specific receptor blocker, on the degree and duration of bronchodilation induced by inhaled ipratropium bromide in patients with COPD. Five clinics and university medical centers in four countries participated in the study; forty seven patients with COPD were randomized to treatment; 44 completed all treatments. Patients had a baseline (pre-bronchodilator) FEV1 > 1 liter and post-bronchodilator (200 mcg salbutamol) FEV1 < 90% of predicted, with FEV1 reversibility (to 80 mcg inhaled ipratropium bromide and 400 mcg salbutamol) of at least 12% or 200 ml over baseline. The study was divided into two parts. In Part A, each patient received in a random order, four-way cross-over manner, single doses of ondansetron placebo (oral) plus ipratropium bromide placebo (inhaled), ondansetron placebo plus ipratropium bromide 40 mcg inhaled via MDI, ondansetron 24 mg oral plus ipratropium bromide placebo and ondansetron 24 mg plus ipratropium bromide 40 mcg. In Part B, each patient received in a random order, two-way crossover manner, ipratropium bromide 40 mcg tid via MDI plus ondansetron 8 mg oral, qid, for two days; on day 3 patients received a single dose of ipratropium bromide 40 mcg plus 8 mg oral ondansetron. Alternatively, patients received ipratropium bromide via MDI and oral ondansetron placebo, as described above. Statistically significant differences in weighted mean FEV1 (0-6 hours), peak FEV1 and FEV1 determined 6 hours post-dose were noted comparing ipratropium bromide to placebo. Similar positive results were observed for sGaw and FVC. Addition of ondansetron to ipratropium bromide did not significantly modify values obtained with ipratropium alone. Ipratropium bromide induced a marked bronchodilation, compared to placebo. Addition of ondansetron (single or repeated doses) did not significanlty increase the degree or duration of A c c e p t e d m a n u s c r i p t 2 bronchodilation induced by ipratropium alone. sGaw was consistently more sensitive than FEV1 in measuring extent and duration of bronchodilation.

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Increased Levels of Free Serotonin in Plasma of Symptomatic Asthmatic Patients

Cited by 120 publications

References 47 publications

Association analysis of DTD1 gene variations with aspirin-intolerance in asthmatics

Association analysis of DTD1 gene variations with aspirin-intolerance in asthmatics

Airway Hyperresponsiveness in Patients With Coronary Spastic Angina Relationship Between Coronary Spasticity and Airway Responsiveness

Bronchodilating effect of combined therapy with ipratropium bromide and ondansetron in patients with COPD

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