title: Temperature and agonist dependency of tachykinin NK1 receptor antagonist potencies in rat isolated superior cervical ganglion.
abstract: Using rat isolated superior cervical ganglion we have further characterised tachykinin NK1 receptors and investigated the possible existence of tachykinin NK1 receptor subtypes. At 37 degrees C, tachykinin NK1 receptor antagonists GR82334 ([D-Pro9[spiro-gamma- lactam]Leu10,Trp11]physalaemin-1(1-11)), CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) and (+/-)-RP67580 (7,7-diphenyl-2[1-imino-2(2-methoxy- phenyl)-ethyl]perhydroisoindol-4-one (3aR,7aR)) antagonised more potently depolarisation responses evoked by GR73632 (delta Ava]L-Pro9,N-MeLeu10]SP-(7-11)), septide ([pGlu6,Pro9]SP-(6-11)) and neurokinin A than those evoked by substance P, substance P O-methyl ester and [Sar9,Met(O2)11]substance P. GR73632 and substance P O-methyl ester evoked depolarisation responses of similar magnitude, unaffected by addition of tetrodotoxin, but which cross-desensitised. At 22 degrees C, the ability of GR82334 and (+/-)-RP67580 to inhibit substance P O-methyl ester-evoked but not GR73632-evoked responses was enhanced greatly. These results suggest a single population of tachykinin NK1 receptors in this preparation. The agonist and temperature dependency of tachykinin NK1 receptor antagonist potency in rat isolated superior cervical ganglion may reflect different conformational changes in the tachykinin NK1 receptor induced by partial or full sequence substance P analogues.
authors.affiliation: Department of Pharmacology, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.
authors.forename: A B
authors.initials: AB
authors.lastname: Hawcock
authors.forename: I J
authors.initials: IJ
authors.lastname: Beresford
authors.forename: F H
authors.initials: FH
authors.lastname: Marshall
authors.forename: R M
authors.initials: RM
authors.lastname: Hagan
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000819:agonists* / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C068032:GR 73632; D013373:Substance P; D013779:Tetrodotoxin; D015288:Neurokinin A