Xp. Zeng et E. Burcher, USE OF SELECTIVE ANTAGONISTS FOR FURTHER CHARACTERIZATION OF TACHYKININ NK-2, NK-1 AND POSSIBLE SEPTIDE-SELECTIVE RECEPTORS IN GUINEA-PIG BRONCHUS, The Journal of pharmacology and experimental therapeutics, 270(3), 1994, pp. 1295-1300
NK-1 and NK-2 tachykinin receptors in guinea pig airways appear to hav
e some unusual characteristics. The analog [pGlu(6),Pro(9)] 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 furth
er the receptors in the guinea pig bronchus. In the presence of 1 mu M
indomethacin and phosphoramidon, the selective agonists [Sar(9),Met(O
-2)(11)]-SP and [Pro(9)]-SP (both NK-1), [Lys(5),MeLeu(9),Nle(10)]-NKA
(4-10) (NK-2) and septide were full agonists, with pD(2) values of 8.0
0, 7.78, 9.11 and 8.52, respectively on epithelium-intact preparations
. Contractions to septide were unaffected by atropine (5 mu M) and tet
rodotoxin (1 mu M). Denudation of epithelium significantly enhanced th
e potency of [Sar(9),Met(O-2)(11)]-SP and [Pro(9)]-SP but not of septi
de and [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10). The potency order for NK-2
-selective antagonists against [Lys(5),MeLeu(9),Nle(11)]-NKA(4-10) was
GR 94800 > SR 48968 MDL 29913 > MEN 10207 (pA(2) 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 [Sar(9),Met(O-
2)(11)]-SP and [Pro(9)]-SP (pA(2) 6.69 or less), whereas they were mor
e than one order of magnitude more potent against septide (pA(2), 7.78
, 7.48 and 6.58, respectively). In epithelium-denuded bronchi, the ant
agonist potency of GR 82334 was unchanged. These data indicate that se
ptide interacts with tachykinin receptors in guinea pig bronchial smoo
th muscle in a manner different from that of [Sar(9),Met(O-2)(11)]-SP
and [Pro(9)]-SP, and provide some evidence for heterogeneity of NK-1 r
eceptors in the guinea pig airways.