Specific agonists for neurokinin B receptors.
A series of analogues of the partial sequence NKB-(4-10) (H-Asp-Phe-Phe-Val-Gly-Leu-Met.NH2) was prepared in an attempt to identify selective agonists for the neurokinin B receptor type. The compounds were tested in the dog carotid artery, the rabbit pulmonary artery and the rat portal vein to evaluate their affinity for the receptors of substance P, neurokinin A and neurokinin B respectively. It has been shown that the replacement of Val7 with MePhe increased significantly the affinity of NKB-(4-10) for the neurokinin B receptor and confered marked selectivity. [MePhe7]NKB-(4-10) was practically inactive as stimulant of the receptor for NKA and was a weak agonist on the receptor for SP. Such significant changes in the pharmacological spectrum of [MePhe7]NKB-(4-10) cannot be attributed to protection from metabolism and appear to be due to changes in the peptide conformation.
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism; D004285:Dogs; D004727:Endothelium / Q000378:metabolism; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D015287:Neurokinin B; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011169:Portal Vein / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D009479:Neuropeptides; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015287:Neurokinin B; C053213:neurokinin B (4-10)