Table 2.
Biological activities of representative NPFF-derived peptidic probes.
Ligand | Sequence | Usage | In vitro activities | In vivo activities |
---|---|---|---|---|
NPFF (a.k.a. F8Fa, 1) | FLFQPQRF-NH2 | Agonist | hNPFFR1 COS-7 or HEK cells Kd = 1.13 nM4 hNPFFR2 COS-7 or HEK cells Kd = 0.21 – 0.37 nM4, 81 Rat spinal cord Ki = 0.21 – 0.34 nM19, 77, 78, 81 hNPFFR2 EC50 = 3.16 nM81 |
Analgesia1, 10, 11, 36–38, 77, 78 Opioid abuse45, 49, 53 Amphetamine abuse55–57 Cocaine abuse58 Cardiovascular activities32, 59, 60, 62 Gastrointestinal mobility74 |
[Tyr1]NPFF (a.k.a. Y8Fa, 2) | YLFQPQRF-NH2 | Agonist | Rat spinal cord Ki = 0.20 nM77 | Pain77 Anorectic effect in fasted mice.82 |
1DMe (3) | [D-Tyr1,(NMe)Phe3] YLFQPQRF-NH2 | Metabolically stable agonist | hNPFFR1 Ki = 2.0 – 7.9 nM4, 80 hNPFFR2 Ki = 3.2 nM4 rNPFFR1 Ki = 1.6 nM4 rNPFFR2 Ki = 2.0 nM4 Rat spinal cord Ki = 0.07 – 034 nM77, 78, 80, 81 hNPFFR2 EC50 = 2.69 nM81 |
Analgesia77
38, 40, 78, 80 Opioid abuse52 Gastrointestinal mobility75 |
Nic-1DMe (4) | [D-Tyr1,(NMe)Phe3,Nic-Pro5] YLFQPQRF-NH2 | Metabolically stable agonist | Rat spinal cord Ki = 0.07 nM80 hNPFFR1 Ki = 1.30 nM80 |
Pain80 |
NPVF (5) | VPNLPQRF-NH2 | NPFFR1 agonist | hNPFFR1 Ki = 0.59 nM23 hNPFFR2 Ki = 23 nM23 |
Cardiovascular activities62 |
dNPA (6) | [D-Asn1,(NMe)Ala3] NPAFLFQPQRF-NH2 | NPFFR2 agonist | hNPFFR1 Ki = 2.9 nM23 hNPFFR2 Ki = 0.027 nM23 |
Cardiovascular activities62 |
FMRFamide (7) | FMRF-NH2 | Agonist | Rat spinal cord Ki = 1.8 nM19 hNPFFR2 Ki = 6.6 nM81 hNPFFR2 EC50 = 517 nM81 |
Pain36 Feeding65 Gastrointestinal mobility74 |
PQRFamide (8) | PQRF-NH2 | Agonist | hNPFFR1 Ki = 40 nM4 Rat spinal cord Ki = 15.5 nM81 hNPFFR2 Ki = 25 nM4 rNPFFR1 Ki = 25 nM4 rNPFFR2 Ki = 25 nM4 hNPFFR2 EC50 = 309 nM81 |
Cardiovascular activities61 |
PFR(Tic)amide (9) | [Tic-Arg3]PFR(Tic)-NH2 (Fig. 1) | NPFFR1 antagonist, NPFFR2 agonist | Rat NPFFR1 Ki = 101 nM56 Rat NPFFR1 IC50 = 0.1 nM56 hNPFFR2 EC50 = 2400 ± 400 nM83 |
Opioid abuse47 Cardiovascular activities61 |
daY8Ra (10) | [desamino-Tyr1]YFLFQPQR-NH2 | Metabolically stable antagonist | Rat spinal cord Ki = 0.20 ± 0.04 nM50 | Opioid addiction50 |
Dansyl-PQRNH2 (11) | [dns-Pro1]PQR-NH2 (Fig. 1) | CNS permeable antagonist | Rat spinal cord Ki = 13 μM84 | Opioid addiction47, 84 |
RF9 (12) | See Fig. 1 | Agonist/ Antagonist | hNPFFR1 Ki = 58 nM32 hNPFFR2 Ki = 75 nM32 |
Pain32 Opioid addiction32 Cardiovascular activities32 |
GJ14 (13) | See Fig. 1 | Antagonist | hNPFFR1 EC50 = 21 nM72 hNPFFR1 EC50 = 387 nM72 |
Anxiety72 |