The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces Ca2+ release in rat mesenteric artery endothelial cells

Y. M. Alsuleimani, C. R. Hiley

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18 Citations (Scopus)

Abstract

Background and Purpose Lysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca2+. Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca2+ responses in endothelial cells isolated from the artery. Experimental Approach Vascular responses were studied using wire myographs. Single-cell fluorescence imaging was performed using a MetaFluor system. Hypotensive effects of LPI were assessed using a Biopac system. Key Results In isolated arteries, LPI-induced vasorelaxation was concentration- and endothelium-dependent and inhibited by CID 16020046, a GPR55 antagonist. The CB1 receptor antagonist AM 251 had no effect, whereas rimonabant and O-1918 significantly potentiated LPI responses. Vasorelaxation was reduced by charybdotoxin and iberiotoxin, alone or combined. LPI decreased systemic arterial pressure. GPR55 is expressed in rat mesenteric artery. LPI caused biphasic elevations of endothelial cell intracellular Ca2+. Pretreatment with thapsigargin or 2-aminoethoxydiphenyl borate abolished both phases. The PLC inhibitor U73122 attenuated the initial phase and enhanced the second phase, whereas the Rho-associated kinase inhibitor Y-27632 abolished the late phase but not the early phase. Conclusions and Implications LPI is an endothelium-dependent vasodilator in the rat small mesenteric artery and a hypotensive agent. The vascular response involves activation of Ca2+-sensitive K+ channels and is not mediated by CB1 receptors, but unexpectedly enhanced by antagonists of the 'endothelial anandamide' receptor. In endothelial cells, LPI utilizes PLC-IP3 and perhaps ROCK-RhoA pathways to elevate intracellular Ca2+. Overall, these findings support an endothelial site of action for LPI and suggest a possible role for GPR55 in vasculature.

Original languageEnglish
Pages (from-to)3043-3057
Number of pages15
JournalBritish Journal of Pharmacology
Volume172
Issue number12
DOIs
Publication statusPublished - Jun 1 2015

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ASJC Scopus subject areas

  • Pharmacology

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