Zeng X P, Burcher E
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
J Pharmacol Exp Ther. 1994 Sep;270(3):1295-300.
NK-1 and NK-2 tachykinin receptors in guinea pig airways appear to have some unusual characteristics. The analog [pGlu6,Pro9] SP(6-11) (septide) may also act on atypical NK-1 receptors in guinea pig ileum. In this study, we used new tachykinin antagonists to investigate further the receptors in the guinea pig bronchus. In the presence of 1 microM indomethacin and phosphoramidon, the selective agonists [Sar9,Met(O2)11]-SP and [Pro9]-SP (both NK-1), [Lys5,MeLeu9,Nle10]-NKA(4-10) (NK-2) and septide were full agonists, with pD2 values of 8.00, 7.78, 9.11 and 8.52, respectively on epithelium-intact preparations. Contractions to septide were unaffected by atropine (5 microM) and tetrodotoxin (1 microM). Denudation of epithelium significantly enhanced the potency of [Sar9,Met(O2)11]-SP and [Pro9]-SP but not of septide and [Lys5,MeLeu9,Nle10]-NKA(4-10). The potency order for NK-2-selective antagonists against [Lys5,MeLeu9,Nle10]-NKA(4-10) was GR 94800 > SR 48968 MDL 29913 > MEN 10207 (pA2 values 8.97, 8.73, 7.11 and 6.49, respectively). The NK-1 selective antagonists, OP 96345, GR 82334 and RP 67580 were weak or ineffective against [Sar9,Met(O2)11]-SP and [Pro9]-SP (pA2 6.69 or less), whereas they were more than one order of magnitude more potent against septide (pA2, 7.78, 7.48 and 6.58, respectively). In epithelium-denuded bronchi, the antagonist potency of GR 82334 was unchanged. These data indicate that septide interacts with tachykinin receptors in guinea pig bronchial smooth muscle in a manner different from that of [Sar9,Met(O2)11]-SP and [Pro9]-SP, and provide some evidence for heterogeneity of NK-1 receptors in the guinea pig airways.
豚鼠气道中的NK-1和NK-2速激肽受体似乎具有一些不寻常的特征。类似物[pGlu6,Pro9]SP(6-11)(septide)也可能作用于豚鼠回肠中的非典型NK-1受体。在本研究中，我们使用新的速激肽拮抗剂进一步研究豚鼠支气管中的受体。在1μM吲哚美辛和磷酰胺存在的情况下，选择性激动剂[Sar9,Met(O2)11]-SP和[Pro9]-SP(均为NK-1)、[Lys5,MeLeu9,Nle10]-NKA(4-10)(NK-2)和septide是完全激动剂，在完整上皮制剂上的pD2值分别为8.00、7.78、9.11和8.52。对septide的收缩不受阿托品(5μM)和河豚毒素(1μM)的影响。上皮剥脱显著增强了[Sar9,Met(O2)11]-SP和[Pro9]-SP的效力，但对septide和[Lys5,MeLeu9,Nle10]-NKA(4-10)没有影响。NK-2选择性拮抗剂对[Lys5,MeLeu9,Nle10]-NKA(4-10)的效力顺序为GR 94800>SR 48968>MDL 29913>MEN 10207(pA2值分别为8.97、8.73、7.11和6.49)。NK-1选择性拮抗剂OP 96345、GR 82334和RP 67580对[Sar9,Met(O2)11]-SP和[Pro9]-SP作用较弱或无效(pA2为6.69或更低)，而它们对septide的效力要强一个数量级以上(pA2分别为7.78、7.48和6.58)。在上皮剥脱的支气管中，GR 82334的拮抗剂效力不变。这些数据表明，septide与豚鼠支气管平滑肌中的速激肽受体相互作用的方式不同于[Sar9,Met(O2)11]-SP和[Pro9]-SP，并为豚鼠气道中NK-1受体的异质性提供了一些证据。
