Paracrine purinergic signaling determines lung endothelial nitric oxide production.

Rainer Kiefmann; Mohammad N Islam; Jens Lindert; Kaushik Parthasarathi; Jahar Bhattacharya

Paracrine purinergic signaling determines lung endothelial nitric oxide production.

Standard

Paracrine purinergic signaling determines lung endothelial nitric oxide production. / Kiefmann, Rainer; Islam, Mohammad N; Lindert, Jens; Parthasarathi, Kaushik; Bhattacharya, Jahar.

in: AM J PHYSIOL-LUNG C, Jahrgang 296, Nr. 6, 6, 2009, S. 901-910.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kiefmann, R, Islam, MN, Lindert, J, Parthasarathi, K & Bhattacharya, J 2009, 'Paracrine purinergic signaling determines lung endothelial nitric oxide production.', AM J PHYSIOL-LUNG C, Jg. 296, Nr. 6, 6, S. 901-910. <http://www.ncbi.nlm.nih.gov/pubmed/19304909?dopt=Citation>

APA

Kiefmann, R., Islam, M. N., Lindert, J., Parthasarathi, K., & Bhattacharya, J. (2009). Paracrine purinergic signaling determines lung endothelial nitric oxide production. AM J PHYSIOL-LUNG C, 296(6), 901-910. [6]. http://www.ncbi.nlm.nih.gov/pubmed/19304909?dopt=Citation

Vancouver

Kiefmann R, Islam MN, Lindert J, Parthasarathi K, Bhattacharya J. Paracrine purinergic signaling determines lung endothelial nitric oxide production. AM J PHYSIOL-LUNG C. 2009;296(6):901-910. 6.

Bibtex

@article{9fcc0f0b66474ea7ab9d606ffb42aa73,

title = "Paracrine purinergic signaling determines lung endothelial nitric oxide production.",

abstract = "Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca(2+) (Ca(2+)cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca(2+)cyt and NO responses in EC. Lung expansion induced Ca(2+)cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca(2+)cyt oscillations to microvascular NO production.",

keywords = "Animals, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Calcium Signaling physiology, Cytosol metabolism, Microcirculation physiology, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Paracrine Communication physiology, Pulmonary Alveoli blood supply, Pulmonary Circulation physiology, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2 genetics, Tyrosine analogs, derivatives, Animals, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Calcium Signaling physiology, Cytosol metabolism, Microcirculation physiology, Nitric Oxide metabolism, Nitric Oxide Synthase Type III metabolism, Paracrine Communication physiology, Pulmonary Alveoli blood supply, Pulmonary Circulation physiology, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2 genetics, Tyrosine analogs, derivatives",

author = "Rainer Kiefmann and Islam, {Mohammad N} and Jens Lindert and Kaushik Parthasarathi and Jahar Bhattacharya",

year = "2009",

language = "Deutsch",

volume = "296",

pages = "901--910",

number = "6",

}

RIS

TY - JOUR

T1 - Paracrine purinergic signaling determines lung endothelial nitric oxide production.

AU - Kiefmann, Rainer

AU - Islam, Mohammad N

AU - Lindert, Jens

AU - Parthasarathi, Kaushik

AU - Bhattacharya, Jahar

PY - 2009

Y1 - 2009

N2 - Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca(2+) (Ca(2+)cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca(2+)cyt and NO responses in EC. Lung expansion induced Ca(2+)cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca(2+)cyt oscillations to microvascular NO production.

AB - Although the vascular bed is a major source of nitric oxide (NO) production, factors regulating the production remain unclear. We considered the role played by paracrine signaling. Determinations by fluorescence microscopy in isolated, blood-perfused rat and mouse lungs revealed that a brief lung expansion enhanced cytosolic Ca(2+) (Ca(2+)cyt) oscillations in alveolar epithelial (AEC) and endothelial (EC) cells, and NO production in EC. Furthermore, as assessed by a novel microlavage assay, alveolar ATP production increased. Intra-alveolar microinfusion of the purinergic receptor antagonist, PPADS, and the nucleotide hydrolyzing enzyme, apyrase, each completely blocked the Ca(2+)cyt and NO responses in EC. Lung expansion induced Ca(2+)cyt oscillations in mice lacking the P2Y1, but not the P2Y2, purinergic receptors, which were located in the perivascular interstitium basolateral to AEC. Prolonged lung expansion instituted by mechanical ventilation at high tidal volume increased EC expression of nitrotyrosine, indicating development of nitrosative stress in lung microvessels. These findings reveal a novel mechanism in which mechanically induced purinergic signaling couples cross-compartmental Ca(2+)cyt oscillations to microvascular NO production.

KW - Animals

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Mutant Strains

KW - Calcium Signaling physiology

KW - Cytosol metabolism

KW - Microcirculation physiology

KW - Nitric Oxide metabolism

KW - Nitric Oxide Synthase Type III metabolism

KW - Paracrine Communication physiology

KW - Pulmonary Alveoli blood supply

KW - Pulmonary Circulation physiology

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Purinergic P2 genetics

KW - Tyrosine analogs

KW - derivatives