Two affinities for a single antagonist at the neuronal NKi tachykinin receptor: Evidence from quantitation of receptor endocytosis

Abstract

1 In smooth muscle contractility assays, many NK] receptor (NKir) antagonists inhibit responses to the neurotransmitter, substance P (SP), and its analogue, septide, with markedly diiTerent potency, leading to the proposal that there is a septide-preferring receptor related to the NK|r. 2 We used fluorescence immunohistochemistry and confocal microscopy to visualize agonistinduced NK,r endocytosis and analyse agonist/antagonist interactions at native NKir in neurons of the myenteric plexus of guinea-pig ileum. 3 SP and septide gave sigmoid log concentration-response curves and were equipotent in inducing NKir endocytosis. 4 The NK,r antagonists, CP-99994 (2S,3S)-3-(2-methoxybenzyl)amino-2-ph..