Characterization of NK-1 receptors in guinea pig and rat brain membranes with NK-1 peptides and a non-peptide antagonist.
The major finding of the present investigation is the demonstration of different NK-1 receptors in rat and guinea pig brain membranes with CP 96345 (non-peptide NK-1 antagonist) and R-544 (NK-1 peptide antagonist). We used [3H][Sar9,Met(O2)11]SP, the highly selective ligand for NK-1 receptor to compare NK-1 binding sites in rat and guinea pig brain membranes. Scatchard analysis revealed the existence of a single population of [3H][Sar9,Met(O2)11]SP binding sites in both preparations. The affinity and the maximal number of binding sites were found closely similar in rat (Kd 2 nM, Bmax = 37 fmol/mg protein) and guinea pig brain membranes (Kd = 3 nM, Bmax = 25 fmol/mg of protein). The order of potency of neurokinins to inhibit [3H][Sar9,Met(O2)11]SP binding from rat brain (SP > NKA > NKB) was found different of that observed on guinea pig brain (SP > NKB > NKA). Results obtained with [Sar9,Met(O2)11]SP, [beta Ala8]NKA(4-10) and [MePhe7]NKB suggest that selective agonists cannot discriminate between NK-1 receptors of different species. Using the non-peptide antagonist CP 96345 and the tripeptide R-544, we found that these two NK-1 antagonists discriminate between rat and guinea pig [3H][Sar9,Met(O2)11]SP binding sites.
D000595:Amino Acid Sequence; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D006168:Guinea Pigs; D008566:Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015287:Neurokinin B / Q000494:pharmacology; D051381:Rats; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
D001713:Biphenyl Compounds; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; C066892:CP 96345