TEMPERATURE AND AGONIST DEPENDENCY OF TACHYKININ NK1 RECEPTOR ANTAGONIST POTENCIES IN RAT ISOLATED SUPERIOR CERVICAL-GANGLION

Using rat isolated superior cervical ganglion we have further characte rised tachykinin NK, receptors and investigated the possible existence of tachykinin NK1 receptor subtypes. At 37 degrees C, tachykinin NK1 receptor antagonists GR82334 ([D-Pro(9)[spiro-gamma-lactam]leu(10),Trp (11) ]physalaemin-(1-1)), CP-99,994 thoxybenzylamino)-2-phenyllamino)- phenylpiperidine and (+/-)RP67580 o-2(2-methoxy-phenyl)-ethyl]perhydro isoindol-4-one (3 aR,7aR)) ant agonised more potently depolarisation r esponses evoked by GR73632 (delta Ava[L-Pro(9),N-MeLeu(10)]SP-(7-11)), septide ([pGlu(6),Pro(9)]SP-(6-11)) and neurokinin A than those evoke d by substance P, substance P O-methyl ester and [Sar(9),Met(O-2)(11)] substance P. GR73632 and substance P O-methyl ester evoked depolarisat ion responses of similar magnitude, unaffected by addition of tetrodot oxin, but which cross-desensitised. At 22 degrees C, the ability of GR 82334 and (+/-)-RP67580 to inhibit substance P O-methyl ester-evoked b ut not GR73632-evoked responses was enhanced greatly. These results su ggest a single population of tachykinin NK1 receptors in this preparat ion. The agonist and temperature dependency of tachykinin NK1 receptor antagonist potency in rat isolated superior cervical ganglion may ref lect different conformational changes in the tachykinin NK1 receptor i nduced by partial or full sequence substance P analogues.