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The nitric oxide-cyclic guanosine monophosphate pathway inhibits the bladder ATP release in response to a physiological or pathological stimulus.

ABSTRACT: The release of ATP from the epithelium of the urinary bladder (urothelium) in response to mechanical/chemical stimuli contributes to the visceral sensation in the micturition reflex. The nitric oxide (NO)-mediated induction of cyclic guanosine monophosphate (cGMP) has been detected in urothelial cells and may inhibit the micturition reflex. However, the function of the NO-cGMP pathway in the regulation of urothelial ATP release remains poorly understood in contrast to its effects on smooth muscles or primary afferent nerves. Therefore, we investigated the relevance of the NO-cGMP pathway to ATP release on the mucosal side in the present study. The administration of l-arginine (NO precursor) or NOC 12 (NO donor) significantly reduced ATP release to the mucosal side at a physiologically normal urine storage pressure (5 cmH₂ O). L-NAME (NO synthase inhibitor) significantly increased the distention-induced release of ATP. The phosphodiesterase-5 inhibitor, sildenafil, which increases cGMP levels, inhibited distention-induced ATP release. Furthermore, sildenafil significantly reduced ATP release in response to the administration of lipopolysaccharide. These results suggest that the NO-cGMP pathway inhibited urothelial ATP release during the storage phase under both physiological and pathological conditions.

SUBMITTER: Okuyama E

PROVIDER: S-EPMC8290832 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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The nitric oxide-cyclic guanosine monophosphate pathway inhibits the bladder ATP release in response to a physiological or pathological stimulus.

Okuyama Eriko E Kawatani Masahito M Hashimoto Junichi J Tanimoto Keisuke K Hashimoto Manabu M Matsumoto-Miyai Kazumasa K

Physiological reports 20210701 14

The release of ATP from the epithelium of the urinary bladder (urothelium) in response to mechanical/chemical stimuli contributes to the visceral sensation in the micturition reflex. The nitric oxide (NO)-mediated induction of cyclic guanosine monophosphate (cGMP) has been detected in urothelial cells and may inhibit the micturition reflex. However, the function of the NO-cGMP pathway in the regulation of urothelial ATP release remains poorly understood in contrast to its effects on smooth muscl ...[more]

PMID: 34288526

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Project description:BackgroundThe cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway is closely associated with myocardial infarction (MI). Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is a key component of this pathway; however, there is currently a lack of clinical evidence linking plasma cGAMP levels to MI.MethodsThis study utilized clinical data from 270 patients diagnosed with coronary heart disease (CHD) at the Second Xiangya Hospital of Central South University. The outcomes included ST-segment elevation and non-ST-segment elevation MI. Univariate and multivariate logistic regression models were used to explore the relationships between plasma cGAMP levels and MI, while restricted cubic spline (RCS) using logistic regression to explore the dose-response relationship.ResultsAmong the 270 patients, the mean plasma cGAMP level was 1352.58 ± 106.02 ng/L and 89 (32.96%) patients were diagnosed with MI. The RCS curves indicated a U-shape association between the cGAMP levels and MI; the risk of MI was negatively correlated with the cGAMP until it hit bottoms at 1352 ng/L. When the cGAMP level exceeded 1352 ng/L, the risk of MI increased significantly (adjusted OR, 1.02; 95% CI: 1.01-1.03). When considering cGAMP as a categorical variable, patients in Tertile 1 and Tertile 3 had a 167% (adjusted OR: 2.67, 95% CI: 1.23-5.78) and 155% (adjusted OR: 2.55, 95% CI: 1.17-5.55) higher risk of MI compared to those in Tertile 2, respectively. These results were consistent across subgroup analyses, notably, a significant interaction by age category was observed in patients with cGAMP ≥ 1352 ng/L, where the positive association was pronounced in the elderly.ConclusionsA U-shaped association exists between cGAMP and MI in the CHD population, with a cutoff point at the cGAMP of 1352 ng/L. Both excessively high and low cGAMP levels are associated with an increased risk of MI, particularly among the elderly with cGAMP ≥ 1352 ng/L. This is the first clinical evidence of the cGAS-cGAMP-STING pathway in metabolic cardiovascular diseases.ClinicaltrialsGov identifierNCT03363035 (Registration date: 2018-01-15).

Dataset Information

The nitric oxide-cyclic guanosine monophosphate pathway inhibits the bladder ATP release in response to a physiological or pathological stimulus.

Publications

The nitric oxide-cyclic guanosine monophosphate pathway inhibits the bladder ATP release in response to a physiological or pathological stimulus.

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