Selective Agonists For Receptors Of Substance-P And Related Neurokinins

Neurokinins and their receptors are a complex system consisting of at least three endogenous agents—substance P (SP), neurokinin A (NKA), and neurokinin B (NKB)—and their corresponding receptor types, respectively, NK‐1, NK‐2, and NK‐3. Investigations on receptors have been made using sensitive and fairly selective pharmacological preparations (the dog carotid artery for the NK‐1, the rabbit pulmonary artery devoid of endothelium for the NK‐2, and the rat portal vein for the NK‐3 receptor), and some natural peptides of mammalian and nonmammalian origin. Because of the nonselectivity of the natural peptides, analogues of the neurokinins have been found that act on one receptor only and show therefore high selectivity. The selective agonists [Sar9, Met(O2)11]SP, [Nle10]NKA (4–10), and [MePhe7]‐NKB have been used successfully for (a) characterizing the three neurokinin receptors, (b) identifying isolated organs whose responses to neurokinins depend on the activation of a single (monoreceptor systems) or of more than one (multireceptor systems) receptor, and (c) elucidating some of the physiological function of the three receptor types. It is suggested that NK‐1 mediate peripheral vasodilatation and exocrine secretions, NK‐2 stimulate bronchial muscles and facilitate the release of catecholamines, and NK‐3 promote the release of acetylcholine in peripheral organs.