Pharmacological effects of the dansylated neuropeptide FF analogues on body temperature and morphine analgesia.
In our previous work, the two putative agonists (dansyl-GSRFamide and dansyl-PQRFamide) and the two putative antagonists (dansyl-GSRamide and dansyl-PQRamide) on neuropeptide FF (NPFF) receptors were synthesized to evaluate the importance of Phe(8) of NPFF. In the present study, these putative NPFF agonists/antagonists containing different N-terminal sequences were further examined for their pharmacological profiles in thermoregulatory and nociceptive tests. The results indicated that the two dansylated agonists potently possessed similar thermoregulation (rank order of potencies: dansyl-GSRFamide>>NPFF>dansyl-PQRFamide) and different modulation of opioid-induced analgesia; in contrast, both of the two putative antagonists exhibited marked hypothermia (rank order of potencies: dansyl-PQRamide>dansyl-GSRamide) and facilitation of morphine analgesia (rank order of potencies: dansyl-PQRamide > dansyl-GSRamide). These data reveal that the difference of the N-terminal residues of the two putative agonists causes their dissociation of pharmacological pro- and anti-opioid effects. In addition, their N-terminal part is important to determine the potency of the dansylated agonists/antagonists. Our work might be helpful to develop a highly potent and fluorescent NPFF ligand.
Fang
Quan
Q
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and State Key Laboratory of Applied Organic Chemistry, and Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
He
Feng
F
Wang
Yi-Qing
YQ
Guo
Jia
J
Zhang
Bang-zhi
BZ
Chen
Qiang
Q
Wang
Rui
R
D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D003619:Dansyl Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement
D003619:Dansyl Compounds; D009479:Neuropeptides; D009842:Oligopeptides; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide