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Life Sci. 2018 Jan 1;192:38-45. doi: 10.1016/j.lfs.2017.11.020. Epub 2017 Nov 16.

Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries.

Author information

1
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicza Str. 2A, 15-089 Białystok, Poland. Electronic address: olga.karpinska1@wp.pl.
2
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Mickiewicza Str. 2A, 15-089 Białystok, Poland.
3
Department of Pharmaceutical Biochemistry, Medical University of Białystok, Mickiewicza Str. 2A, 15-089 Białystok, Poland.
4
Department of Inorganic and Analytical Chemistry, Medical University of Białystok, Mickiewicza Str. 2D, 15-222 Białystok, Poland.
5
Department of Thoracic Surgery, Medical University of Białystok, M. Skłodowskiej-Curie Str. 24A, 15-276 Białystok, Poland.
6
Department of Histology and Cytophysiology, Medical University of Białystok, Mickiewicza Str. 2C, 15-222 Białystok, Poland.

Abstract

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.

KEYWORDS:

GPR55; Human pulmonary artery; Vasorelaxation; l-Alpha-lysophosphatidylinositol

PMID:
29155298
DOI:
10.1016/j.lfs.2017.11.020
[Indexed for MEDLINE]

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