EVIDENCE FOR TACHYKININ NK-2 RECEPTORS IN GUINEA-PIG AIRWAYS FROM BINDING AND FUNCTIONAL-STUDIES, USING [I-125] [LYS(5),TYR(I-2)(7),MELEU(9),NIE(10)]-NKA(4-10)
Xp. Zeng et al., EVIDENCE FOR TACHYKININ NK-2 RECEPTORS IN GUINEA-PIG AIRWAYS FROM BINDING AND FUNCTIONAL-STUDIES, USING [I-125] [LYS(5),TYR(I-2)(7),MELEU(9),NIE(10)]-NKA(4-10), Neuropeptides, 26(1), 1994, pp. 1-9
The potent contractile responses of guinea-pig airways to neurokinin A
(NKA) and neuropeptide gamma (NPgamma) are thought to be mediated by
NK-2 receptors. However, NK-2 binding sites are not detectable using t
he radioligand [I-125]-iodohistidyl-NKA. Here, a novel, highly selecti
ve iodinated radioligand, [I-125]-[Lys5,Tyr(I2)7, MeLeu9,Nle10]-NKA(4-
10), and a number of related peptides have been used to characterize N
K-2 receptors on guinea-pig airways, using binding and functional stud
ies. Specific binding of [I-125]-[Lys5,Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10
), was saturable and to a single high affinity site, with K(D) 1.29 +/
- 0.36 nM (n = 4). The rank order of potency for tachykinins and analo
gues as competitors for the binding was: [Lys5,Tyr(I2)7,MeLeu9,Nle10]-
NKA(4-10) greater-than-or-equal-to NPgamma greater-than-or-equal-to [L
ys5,MeLeu9,Nle10]-NKA(4-10) > NKA greater-than-or-equal-to SR 48968 >>
MDL 29913 greater-than-or-equal-to substance P (SP) = [I-127]-Bolton-
Hunter NKA (BHNKA) greater-than-or-equal-to MEN 10207 > neurokinin B (
NKB). Septide, [DPro9,Pro10,Trp11]-SP, the NK-1 selective ligands [Sar
9,Met(O2)11]-SP, [Pro9]-SP and CP 96345, the NK-3 selective senktide,
and calcitonin gene-related peptide (CGRP) were weak or ineffective. O
n guinea-pig isolated bronchi, the potency order of contractile agonis
ts was: [Lys5,MeLeu9,Nle10]-NKA(4-10) > NKA greater-than-or-equal-to N
Pgamma greater-than-or-equal-to [Lys5,Tyr7,MeLeu9, Nle10]-NKA(4-10) gr
eater-than-or-equal-to septide = BHNKA greater-than-or-equal-to [Lys5,
Tyr(I2)7,MeLeu9,Nle10]-NKA(4-10) greater-than-or-equal-to [Sar9,Met(O2
)11]-SP greater-than-or-equal-to NKB = [Pro9]-SP greater-than-or-equal
-to SP >> senktide. All NK-2 receptor preferring agonists, except BHNK
A, had similar potencies in both systems. In conclusion, binding sites
for [I-125]-[Lys5,Tyr(I2)7, MeLeu9,Nle10]-NKA(4-10) probably represen
t the NK-2-like receptors mediating contractions to NK-2 preferring ta
chykinins. NK-1 receptors also mediate contractile responses but NK-3
receptors appear to be negligible in this tissue.