The constitutive activity of ghrelin receptors is decreased by co-expression with vasoactive prostanoid receptors when over-expressed in human embryonic kidney 293 cells.
The functional activity of G protein-coupled receptors can be modified by their ability to form oligomeric complexes with G protein-coupled receptors from other receptor families. Emerging evidence suggests that the appetite-regulating hormone ghrelin is a directly acting vasodilator peptide with anti-inflammatory activity, therefore, we have examined the ability of ghrelin receptors to oligomerize with members of the prostanoid receptor family which are also involved in modulating vascular activity and inflammatory responses. Using the techniques of bioluminescence resonance energy transfer and co-immunoprecipitation, we detected the ability of ghrelin receptors to hetero-oligomerize with prostaglandin E2 receptor subtype EP3-I, prostacyclin receptors, and thromboxane A2 (TPalpha) receptors, when transiently over-expressed in human embryonic kidney 293 cells. These results suggest that hetero-oligomeric interactions between ghrelin receptors and prostanoid receptors are likely to be of biological relevance. Co-transfection of cells with ghrelin receptor and prostanoid receptors significantly decreased ghrelin receptor expression and attenuated its constitutive activation of phospholipase C without changing its affinity for ghrelin. We also observed an increase in the proportion of ghrelin receptors localized intracellularly in the presence of prostanoid receptors. Taken together, these results suggest that the increased expression of prostanoid receptors in conditions of vascular inflammation, such as in atherosclerotic plaques, could influence those cellular responses dependent on the constitutive activation of ghrelin receptors.
Chow
Kevin B S
KB
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Leung
Po-Ki
PK
Cheng
Christopher H K
CH
Cheung
Wing-Tai
WT
Wise
Helen
H
D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
C545647:PTGER3 protein, human; C113936:PTGIR protein, human; D020033:Protein Isoforms; D044006:Receptors, Epoprostenol; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D011993:Recombinant Fusion Proteins; D010738:Type C Phospholipases