Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule.
The cloning of novel G protein-coupled receptors and the search for their natural ligands, a process called reverse pharmacology, is an excellent opportunity to discover novel hormones and neurotransmitters. Based on a degenerate primer approach we have cloned a G protein-coupled receptor whose mRNA expression profile indicates highest expression in the dorsal root ganglia, specifically in the subset of small neurons, suggesting a role in nociception. In addition, moderate expression was found in lung, hypothalamus, peripheral blood leukocytes, and ovaries. Guided by a receptor-activation bioassay, we identified adenine as the endogenous ligand, which activated the receptor potently and with high structural stringency. Therefore, we propose to name this receptor as the adenine receptor. Hormonal functions have already been demonstrated for adenine derivatives like 6-benzylaminopurine in plants and 1-methyladenine in lower animals. Here, we demonstrate that adenine functions as a signaling molecule in mammals. This finding adds a third family besides P1 and P2 receptors to the class of purinergic receptors.
Bender
Eckhard
E
Department of Advanced Bio-Technologies, Johnson and Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Buist
Arjan
A
Jurzak
Mirek
M
Langlois
Xavier
X
Baggerman
Geert
G
Verhasselt
Peter
P
Ercken
Martine
M
Guo
Hong-Qing
HQ
Wintmolders
Cindy
C
Van den Wyngaert
Ilse
I
Van Oers
Irma
I
Schoofs
Liliane
L
Luyten
Walter
W
D000225:Adenine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D011983:Receptors, Purinergic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013552:Swine
D017931:DNA Primers; D018076:DNA, Complementary; D011983:Receptors, Purinergic; C459899:adenine receptor, rat; D019204:GTP-Binding Proteins; D000225:Adenine