Neurokinin receptors antagonists: old and new.
Four neurokinin antagonists of different size have been used to counteract the myotropic effects of substance P, neurokinin A and neurokinin B in isolated organs containing a single receptor type (monoreceptor systems). These are: the dog carotid artery, the rabbit jugular and cava veins and the guinea pig ileum (NK-1), the rabbit pulmonary artery (NK-2) and the rat portal vein (NK-3). Undeca and octapeptides containing 2 D-Trp residues in their sequences were slightly more active on the NK-1, than on the NK-2 and NK-3 receptors and showed little selectivity. In contrast, compound AcThr-D.Trp(For)-Phe.NMe Bz was found to be as good an antagonist as the larger compounds and showed some selectivity for the NK-1 receptors. When tested against kinins or angiotensin, all compounds were found to be inactive, suggesting that they are specific for neurokinins. The present results show that NK-1 receptor antagonism can be obtained with compounds of different size, including tripeptides and nonpeptides.
Jukic
D
D
Department of Pharmacology, Medical School, University of Sherbrooke, Quebec, Canada.
Rouissi
N
N
Laprise
R
R
Boussougou
M
M
Regoli
D
D
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006168:Guinea Pigs; D007700:Kinetics; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*
D000700:Analgesics; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B