Direct evidence for the interaction of neurokinin A with the tachykinin NK(1) receptor in tissue.
Neurokinin A (NKA) is a tachykinin peptide that binds with high affinity to the tachykinin NK(2) receptor. Recent homologous binding studies, however, have shown that neurokinin A is also a high-affinity ligand for the tachykinin NK(1) receptor. In this report, we demonstrate that a photoreactive neurokinin A analogue specifically labels the NK(1) 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 NK(1) receptor in vivo and elicit NK(1) receptor-mediated physiological responses.
Bremer
A A
AA
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Box 388, 715 Albany Sreet, Boston, MA 02118, USA. abremer@bu.edu
Tansky
M F
MF
Wu
M
M
Boyd
N D
ND
Leeman
S E
SE
D000818:Animals; D001667:Binding, Competitive; D007211:Indoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D054833:Isoindoles; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D015288:Neurokinin A / Q000378:metabolism* / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D019920:Photoaffinity Labels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology
D007211:Indoles; D007457:Iodine Radioisotopes; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D019920:Photoaffinity Labels; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D010649:Phenylalanine; D015288:Neurokinin A; C053764:benzoylphenylalanine