JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse.
We recently reported that H-Lys psi (CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV 449), a pseudopeptide analogue of neurotensin-(8-13) with a reduced CH2NH bond in position 8-9, was about 3 times more potent than neurotensin in binding to mouse brain membranes and in contracting the guinea-pig ileum, and was markedly more resistant to degradation than neurotensin when exposed to rat brain membranes. In the present study, we compared the time courses and dose-response relationships for the ability of i.c.v. injected neurotensin and JMV 449 to elicit hypothermia and analgesia (tail-flick test) in the mouse. The results show that the pseudopeptide analogue behaved as a highly potent and long-lasting neurotensin agonist in these two in vivo bioassays. The analogue should prove very useful for studying the effects of chronic neurotensin receptor stimulation in vitro and in vivo.
Dubuc
I
I
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Université de Nice-Sophia Antipolis, Valbonne, France.
Costentin
J
J
Doulut
S
S
Rodriguez
M
M
Martinez
J
J
Kitabgi
P
P
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D009842:Oligopeptides; C077827:JMV 449; D009496:Neurotensin