Receptors for substance P. II. Classification by agonist fragments and homologues.
Substance P (SP), a series of C-terminal fragments, SP-(2-11), SP-(3-11), SP-(4-11), SP-(5-11), SP-(6-11), SP-(7-11) and the homologues physalaemin, eledoisin and kassinin were used to measure the order of potency of agonists in five pharmacological preparations. These are: the guinea pig ileum, the guinea pig trachea, the rabbit mesenteric vein, the dog common carotid artery and the rabbit aorta. Apparent affinities (pD2) and relative activities of SP-related peptides were measured in the absence and presence of antagonists (a mixture of atropine, indomethacin and diphenhydramine) in the guinea pig ileum and the rabbit mesenteric vein, in the absence and presence of indomethacin in the guinea pig trachea and in tissues with intact endothelium (the dog carotid artery and the rabbit aorta). The orders of potency measured in the absence and presence of antagonists in the guinea pig ileum were different, while no major changes were noted in two other preparations, namely the guinea pig trachea and the rabbit mesenteric vein. The order of potency of agonists determined with homologues revealed the existence of three major patterns namely: kassinin greater than eledoisin greater than physalaemin = SP in the guinea pig trachea and the rabbit mesenteric vein, SP = physalaemin greater than eledoisin greater than kassinin in the arterial smooth muscle of the dog carotid artery and the rabbit aorta and physalaemin greater than kassinin greater than eledoisin greater than SP in the guinea pig ileum treated with antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004285:Dogs; D004600:Eledoisin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D015286:Kassinin; D008297:Male; D009130:Muscle, Smooth / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010803:Physalaemin / Q000494:pharmacology; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013329:Structure-Activity Relationship; D013373:Substance P / Q000494:pharmacology*; D014132:Trachea / Q000502:physiology
D009842:Oligopeptides; D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D010803:Physalaemin; D013373:Substance P; D015286:Kassinin; D004600:Eledoisin