
Buprenorphine‐elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ‐, μ‐opioid and nociceptin receptors
Author(s) -
Wang PeiChen,
Ho IngKang,
Lee Cynthia WeiSheng
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12644
Subject(s) - nop , nociceptin receptor , receptor , opioid receptor , opioid , chemistry , pharmacology , opioid peptide , biology , biochemistry
Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ‐ ( KOP ), μ‐opioid ( MOP ) and nociceptin/opioid receptor‐like 1 ( NOP ) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously ( MOP , NOP , and MOP + NOP ) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP , MOP and NOP receptors individually or simultaneously ( KOP , KOP + MOP , KOP + NOP and KOP + MOP + NOP ). Radioligand binding with tritium‐labelled diprenorphine confirmed the expression of KOP receptors. Immunoblotting and immunocytochemistry indicated that the expressed KOP , MOP and NOP receptors are N ‐linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists— U‐69593, DAMGO and nociceptin— inhibited adenylate cyclase ( AC ) activity in cells expressing KOP , MOP and NOP receptors respectively. Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP + MOP + NOP receptors. Chronic exposure to buprenorphine induced concentration‐dependent AC superactivation in cells expressing KOP + NOP receptors, and the level of this superactivation was even higher in KOP + MOP + NOP ‐expressing cells. Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration‐dependent AC superactivation elicited by chronic buprenorphine exposure.