Increased abundance of opioid receptor heteromers after chronic morphine administration.
The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction.
Gupta
Achla
A
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Mulder
Jan
J
Gomes
Ivone
I
Rozenfeld
Raphael
R
Bushlin
Ittai
I
Ong
Edmund
E
Lim
Maribel
M
Maillet
Emeline
E
Junek
Mats
M
Cahill
Catherine M
CM
Harkany
Tibor
T
Devi
Lakshmi A
LA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000906:Antibodies; D046912:Multiprotein Complexes; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine; D000262:Adenylyl Cyclases