Can it be?

By Jef Akst Can it be? Courtesy of Huei-Ying Chen, Ken Mackie, & Hui-Chen Lu The paper: E. Ryberg et al., “The orphan receptor GPR55 is a novel cannabinoid receptor,” British Journal of Pharmacology, 152:1092–101. (Cited in 99 papers) The finding: Expressing the orphan receptor GPR55 on the membranes of human embryonic kidney cells, biochemist Peter Greasley and his colleagues at AstraZeneca discovered that it b

Jef Akst
Jef Akst

Jef Akst is managing editor of The Scientist, where she started as an intern in 2009 after receiving a master’s degree from Indiana University in April 2009 studying the mating behavior of seahorses.

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Nov 1, 2009

Can it be?

Courtesy of Huei-Ying Chen, Ken Mackie, & Hui-Chen Lu

The paper:

E. Ryberg et al., “The orphan receptor GPR55 is a novel cannabinoid receptor,” British Journal of Pharmacology, 152:1092–101. (Cited in 99 papers)

The finding:

Expressing the orphan receptor GPR55 on the membranes of human embryonic kidney cells, biochemist Peter Greasley and his colleagues at AstraZeneca discovered that it bound many of the same ligands as CB1 and CB2, the two known cannabinoid receptors. “It raised the question of whether [GPR55] might be [another] cannabinoid receptor,” says pharmacologist Roger Pertwee of the University of Aberdeen in Scotland, potentially serving as a novel drug target to suppress inflammation, for example.

The difference:

While GPR55 was bound by a number of the same ligands known to bind CB1 and CB2—including the principle psychoactive component of cannabis (Δ9-THC)—it was also activated by other ligands, including one that made CB1...

The follow-up:

More recent studies of GPR55 have yielded “a real mix,” Greasley admits, largely a result of methodological differences. Some have suggested that cannabinoid ligands do not activate GPR55. “It’s all in a state of confusion right now,” Pertwee says.

The jury:

Part of the problem stems from the “very loose definition” of “cannabinoid receptor,” says Pertwee. To address this issue, the International Union of Basic and Clinical Pharmacology has assembled a committee to discuss the definition. “We will have to come up with some kind of consensus,” says committee member Pertwee.

EC50 (nM), ligand concentration that generates half the receptor’s maximal effect
Cocktail GPR55 CB1 CB2
Δ 9-THC 8 6 0.4
Anandamide (an endocannabinoid) 18 31 27

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