Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries
In: Life Sciences, Jg. 192 (2018), S. 38-45
Online
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Zugriff:
Aims l -Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs). Main methods Functional studies were performed in isolated hPAs using organ bath technique. The expression of GPR55 in hPAs and bronchioles was determined by real-time qPCR, Western blot analysis, and immunohistochemistry. Key findings LPI induced a concentration-dependent vasorelaxation in endothelium-intact hPAs. This effect was attenuated by the GPR55 antagonist CID16020046, the peroxisome proliferator-activated receptor-γ (PPARγ) antagonist GW9662, the putative endothelial cannabinoid receptor (CBe) antagonist O-1918 and the inhibitor of nitric oxide (NO) synthase (L-NAME). In addition, vasorelaxation was also attenuated by the presence of a high KCl concentration, selective blockers of small (KCa2.3; UCL1684), intermediate (KCa3.1; TRAM-34) and large conductance (KCa1.1; iberiotoxin) calcium-activated potassium channels and by endothelium denudation. However, vasorelaxation was not attenuated by the cannabinoid CB1 receptor antagonist AM251 or by the cyclooxygenase inhibitor indomethacin. Significance The study showed that the LPI-induced vasorelaxation was endothelium-dependent and mediated by GPR55, PPARγ and CBe receptors, occurred in a NO- and calcium-activated potassium channel-dependent manner in isolated hPAs. LPI seems to possess positive, hypotensive properties in pulmonary vascular bed.
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Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries
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Autor/in / Beteiligte Person: | Baranowska-Kuczko, Marta ; Kozłowska, Hanna ; Kusaczuk, Magdalena ; Golec, Paweł ; Gęgotek, Agnieszka ; Kloza, Monika ; Kasacka, Irena ; Malinowska, Barbara ; Karpińska, Olga |
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Zeitschrift: | Life Sciences, Jg. 192 (2018), S. 38-45 |
Veröffentlichung: | Elsevier BV, 2018 |
Medientyp: | unknown |
ISSN: | 0024-3205 (print) |
DOI: | 10.1016/j.lfs.2017.11.020 |
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