Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GPR55 is a seven-transmembrane G-protein-coupled receptor that has been proposed as a novel type of cannabinoid receptor. Previously, we identified lysophosphatidylinositol (LPI), in particular 2-arachidonoyl-LPI, as an agonist for GPR55. In the present study, we examined whether intracellular phospholipase A1 (DDHD domain containing 1, or DDHD1), previously identified as phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), is involved in the formation of 2-arachidonoyl-LPI. HEK293 cells expressing DDHD1 produced [(3)H]arachidonic acid-containing LPI after prelabeling with [(3)H]arachidonic acid and subsequent activation by ionomycin; the formation of [(3)H]LPI was inhibited by n-butanol and the overexpression of an inactive PLD1 mutant PLD1K898R. DDHD1 was translocated from the cytosol to membranes upon ionomycin treatment. A purified recombinant DDHD1 formed [(3)H]LPI when incubated with [(3)H]PI; the V(max) and apparent K(m) were 190 micromol/min/mg protein and 10 mol% PI, respectively. DDHD1 binds PA, and the addition of PA to DDHD1 increased the affinity for PI (K(m) ; 3 mol%) and augmented the PI-PLA1 activity. DDHD1 activated by PA was returned to a basal state by its own PA-hydrolytic activity. These results implicate DDHD1 in the formation of 2-arachidonoyl-LPI and indicate that the process is modulated by PA released by phospholipase D. Similar observations for the production of arachidonic acid-containing LPI in neuroblastoma cells suggest the DDHD1-LPI-GPR55 axis to be involved in functions in the brain.
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PMID:Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1. 2035 46

Lysophosphatidylinositol (LPI) is a subspecies of lysophospholipid and is assumed to be not only a degradation product of phosphatidylinositol (PI), but also a bioactive lysophospholipid mediator. However, not much attention has been directed toward LPI compared to lysophosphatidic acid (LPA), since the receptor for LPI has not been identified. During screening for an agonist for the orphan G protein coupled receptor GPR55, we identified LPI, 2-arachidonoyl LPI in particular, as an agonist for GPR55. Our efforts to identify an LPI receptor facilitated research on LPI as a lipid messenger. In addition, we also found that DDHD1, previously identified as phosphatidic acid-preferring phospholipase A1, was one of the synthesizing enzymes of 2-arachidonoyl LPI. Here, we summarized the background for discovering the LPI receptor, and the actions/metabolism of LPI. We also referred to the biosynthesis of PI, a 1-stearoyl-2-arachidonoyl species, since the molecule is the precursor of 2-arachidonoyl LPI. Furthermore, we discussed physiological and/or pathophysiological processes involving LPI and GPR55, including the relevance of LPI-GPR55 and cannabinoids, since GPR55 was previously postulated to be another cannabinoid receptor. Although there is no doubt that GPR55 is the LPI receptor, we should re-consider whether or not GPR55 is in fact another cannabinoid receptor.
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PMID:The actions and metabolism of lysophosphatidylinositol, an endogenous agonist for GPR55. 2371