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Previously, we investigated its effects in an\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    model expressing human\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors individually or simultaneously (\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    , and\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    ) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors individually or simultaneously (\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    ). Radioligand binding with tritium\u2010labelled diprenorphine confirmed the expression of\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    receptors. Immunoblotting and immunocytochemistry indicated that the expressed\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors are\n                    <jats:italic>N<\/jats:italic>\n                    \u2010linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists\u2014 U\u201069593,\n                    <jats:styled-content style=\"fixed-case\">DAMGO<\/jats:styled-content>\n                    and nociceptin\u2014 inhibited adenylate cyclase (\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    ) activity in cells expressing\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors respectively. Buprenorphine, when applied acutely, inhibited\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    activity to ~90% in cells expressing\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors. Chronic exposure to buprenorphine induced concentration\u2010dependent\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    superactivation in cells expressing\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors, and the level of this superactivation was even higher in\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    +\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    \u2010expressing cells. Our study demonstrated that\n                    <jats:styled-content style=\"fixed-case\">MOP<\/jats:styled-content>\n                    receptor could enhance\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    regulation in the presence of coexpressed\n                    <jats:styled-content style=\"fixed-case\">KOP<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptors, and\n                    <jats:styled-content style=\"fixed-case\">NOP<\/jats:styled-content>\n                    receptor is essential for concentration\u2010dependent\n                    <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>\n                    superactivation elicited by chronic buprenorphine exposure.\n                  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