Direct evidence for the interaction of neurokinin A with the tachykinin NK₁ receptor in tissue

Neurokinin A (NKA) is a tachykinin peptide that binds with high affinity to the tachykinin NK₂ receptor. Recent homologous binding studies, however, have shown that neurokinin A is also a high-affinity ligand for the tachykinin NK₁ receptor. In this report, we demonstrate that a photoreactive neurokinin A analogue specifically labels the NK₁ receptor in rat submandibular gland membranes and show via bioassay that neurokinin A is a potent stimulator of salivary secretion. Through the use of specific non-peptide antagonists in both photolabeling and functional assays, we unequivocally demonstrate that neurokinin A can specifically interact with the NK₁ receptor in vivo and elicit NK₁ receptor-mediated physiological responses.