Life sciences · 2017
Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries.
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Karpińska Olga, Baranowska-Kuczko Marta, Malinowska Barbara, Kloza Monika, Kusaczuk Magdalena, Gęgotek Agnieszka, Golec Paweł, Kasacka Irena, Kozłowska Hanna
Аннотация
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.
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.
Предметные рубрики MeSH
AgedAnilidesAnisolesAzabicyclo CompoundsBenzoatesBronchiolesCyclohexanesDose-Response Relationship, DrugEndothelium, VascularEnzyme InhibitorsFemaleHumansIn Vitro TechniquesLysophospholipidsMaleMiddle AgedMuscle RelaxationMuscle, Smooth, VascularNG-Nitroarginine Methyl EsterPPAR gammaPotassium Channel BlockersPulmonary ArteryReceptors, CannabinoidReceptors, G-Protein-Coupled