Mechanisms of L-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries

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-gamma (PPAR gamma)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 (K(Ca)2.3; UCL1684), intermediate (K(Ca)3.1; TRAM-34) and large conductance (K(Ca)1.1; 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, PPAR. 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.