The nonpeptide NK-2 antagonist SR 48968 is also a NK-3 antagonist in the guinea but not in the rat.
SR 48968 was first described as a NK-2 nonpeptide receptor antagonist; we report here that SR 48968 interacts also with guinea pig but not rat NK-3 cortical binding sites. Furthermore, SR 48968 is shown to inhibit the senktide- (a NK-3 selective agonist) evoked stimulation of phosphoinositide turnover in guinea pig ileum slices. The species difference observed for the NK-3 receptor with SR 48968 was confirmed by the determination of the affinities of NK-3 peptide agonists. [Pro7]neurokinin B particularly was found to have a greater affinity for cortical NK-3 binding sites in the rat than in the guinea pig.
Petitet
F
F
Collège de France, INSERM U 114, Paris.
Beaujouan
J C
JC
Saffroy
M
M
Torrens
Y
Y
Glowinski
J
J
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004789:Enzyme Activation; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D015288:Neurokinin A / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*; D015320:Tachykinins / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D001549:Benzamides; D010446:Peptide Fragments; D010716:Phosphatidylinositols; D010880:Piperidines; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; C054724:senktide; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D010738:Type C Phospholipases