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Table 1.

Evaluation of CPS emitted in NOP/RLuc expressing membranes in presence of 1 or 10 μM of following compounds.

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Table 1 Expand

Fig 1.

Light emitted (CPS) as function of the amount of protein (μg) in membranes prepared from NOP/RLuc cells expressing either Gβ1/RGFP or β-arrestin 2/RGFP membranes.

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Fig 1 Expand

Fig 2.

Concentration-response curves to N/OFQ—experiments performed in absence and in presence of PTX 10 ng 20 h treatment.

NOP/G-protein (left panel) and NOP/β-arrestin 2 interaction experiments (right panel). Data are mean ± sem of 3 separate experiments performed in duplicate.

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Fig 2 Expand

Table 2.

Potencies (pEC50), concentration ratio (CR), and maximal effects (Emax) of the compounds tested on the interaction of NOP with G protein and β-arrestin 2.

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Table 2 Expand

Fig 3.

NOP receptor/G-protein interaction experiments—Concentration-response curves to N/OFQ (Panel A); N/OFQ, UFP-112, PWT2-N/OFQ, N/OFQ(1–13)-NH2, and [Arg14Lys15]N/OFQ (Panel B); N/OFQ, SCH-221510, and Ro 65–6570 (Panel C); N/OFQ, UFP-113, UFP-101, [F/G]N/OFQ(1–13)-NH2, [Nphe1]N/OFQ(1–13)-NH2, and Ac-RYYRIK-NH2 (Panel D).

Data are expressed as mean ± sem of at least 5 separate experiments performed in duplicate.

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Fig 3 Expand

Fig 4.

NOP receptor/G protein interaction experiments—concentration-response curves to N/OFQ in absence and in presence of C-24, UFP-101, and J-113397.

Data are mean ± sem of 5 separate experiments performed in duplicate.

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Fig 4 Expand

Table 3.

Effects on NOP/G protein and NOP/β-arrestin 2 interactions of NOP ligands showing reduced efficacy.

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Table 3 Expand

Fig 5.

NOP receptor / G protein interaction experiments—concentration-response curves to N/OFQ in absence and in presence of increasing concentrations (1–100 nM) of SB-612111 (left panel).

The corresponding Schild plot is shown in the middle panel. The inhibition response curve to SB-612111 vs. N/OFQ 30 nM is shown in the right panel. Data are mean ± sem of 4 separate experiments performed in duplicate.

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Fig 5 Expand

Fig 6.

NOP receptor/β-arrestin 2 interaction experiments—Concentration-response curves to N/OFQ (Panel A); N/OFQ, UFP-112, PWT2-N/OFQ, N/OFQ(1–13)-NH2, [Arg14Lys15]N/OFQ (Panel B); N/OFQ, SCH-221510, and Ro 65–6570 (Panel C); N/OFQ, UFP-113, UFP-101, [F/G]N/OFQ(1–13)-NH2, [Nphe1]N/OFQ(1–13)-NH2, and Ac-RYYRIK-NH2 (Panel D).

Data are expressed as mean ± sem of at least 5 separate experiments performed in duplicate.

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Fig 6 Expand

Fig 7.

NOP receptor / β-arrestin 2 protein interaction experiments—concentration-response curves to N/OFQ in absence and in presence of SB-612111 (100 nM, panel A), C-24 (10 nM, panel B), [F/G]N/OFQ(1–13)-NH2 (300 nM, panel C), Ac-RYYRIK-NH2 (300 nM, panel D), J-113397 (300 nM, panel E), UFP-101 (1 μM, panel F), UFP-113 (30 nM, panel G), and [Nphe1]N/OFQ(1–13)-NH2 (1 μM, panel H).

Data are mean ± sem of at least 3 separate experiments performed in duplicate.

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Fig 7 Expand

Table 4.

Bias factors obtained from at least 5 independent Emax/EC50 values from both NOP/G-protein and NOP/arrestin experiments.

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Table 4 Expand