New selective agonists for neurokinin receptors: pharmacological tools for receptor characterization

Section: Introductionmentioning

confidence: 90%

Tachykinin‐induced contraction of the guinea‐pig isolated oesophageal mucosa is mediated by NK₂ receptors

Kerr

Thai

Coupar

2000

“…These results indicate the bronchoconstriction was predominantly mediated via NK2 receptors. For further evaluation of these data, we compared the responses to the endogenous ligand, NKA, which has a more dominant effect on NK2 receptors but can also activate other tachykinin receptors (NK, and NK3) (Drapeau et al, 1987), and the synthetic selective NK2 agonist Me'°NKA(4-10) (Regoli et al, 1988 (Lou et al, 1991). Hence the capsaicin-induced bronchoconstriction was more resistant to SR 48968 or DAC , than that induced by vagal stimulation.…”

Section: Discussionmentioning

confidence: 99%

Postjunctional inhibitory effect of the NK₂ receptor antagonist, SR 48968, on sensory NANC bronchoconstriction in the guinea‐pig

Lou

Lee

Satoh

et al. 1993

1 The effects of a selective NK2 receptor antagonist, SR 48968, on non-adrenergic non-cholinergic (NANC) bronchoconstriction in the guinea-pig were investigated in both in vitro and in vivo studies. 2 In isolated bronchus, the electrical field stimulation (EFS, 1 Hz for 1 min)-induced NANC bronchoconstriction was inhibited by 83% after preincubation with SR 48968 (l0-7 M) for 1 h. The selective NK1 receptor antagonist, CP 96,345 (10-6 M), together with SR 48968 completely abolished the remaining EFS-evoked NANC bronchial contraction. ST 48968 (10-7 M) totally blocked the bronchial contraction caused by neurokinin A (NKA), but reduced only slightly the bronchoconstriction caused by high concentrations of substance P (SP) and did not influence the response to acetylcholine (ACh). 3 In the guinea-pig isolated perfused lung, SR 48968 (5 x I0-M) perfusion for 30 min markedly reduced, by 95% and 68% respectively, the increase in lung resistance (RL) and the decrease in dynamic compliance (CDyfl) evoked by vagal stimulation (1 Hz for 1 min). Capsaicin (10-8 M)-evoked bronchoconstriction was also significantly inhibited by SR 48968 (5 x 10-7 M). However, the same concentration of SR 48968 did not affect the release of neuropeptide calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) evoked by either vagal stimulation or capsaicin in the isolated perfused lung, suggesting no prejunctional action. SR 48968 (5 x 10-7 M) caused a parallel shift of the concentrationresponse curve to the right by a factor of 10 for the bronchoconstriction evoked by NKA (l0-9-3 x 10-7 M) in the isolated lung, while it abolished the contraction induced by the selective NK2 receptor agonist, Nle'°NKA(4-10) (10--3 x 10-7 M).

“…izing TK receptors which mediate a particular response has been greatly facilitated by the development of synthetic TK analogues which possess strong or even absolute selectivity for one particular TK receptor Drapeau et al, 1987;Regoli et al, 1988;Rovero et al, 1989). These synthetic analogues have been fruitfully employed to characterize specific TK receptors in various bioassays (Giuliani et al, 1988;Devillier et al, 1988;Maggi et al, 1989a,b,c;Patacchini et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

NK₁‐receptors mediate the proliferative response of human fibroblasts to tachykinins

Ziche¹,

Morbidelli

Pacini

et al. 1990

102

1The effect of synthetic tachykinin selective receptor agonists was studied on the growth of cultured human skin fibroblasts (HF). 2 Human fibroblasts were grown in serum-free conditions in the presence of natural tachykinins (substance P and neurokinin A) and of three synthetic agonists, [fl-Ala4, Sar9, Met (02) Cell proliferation was measured by percentage increase in cell number and by [3H]-thymidine uptake following 48 h exposure to agents compared to baseline condition. 3 Neurokinin A (NKA) and substance P (SP) significantly increased cell proliferation the threshold concentrations being 10-12 and 10-11 M, respectively. Addition of thiorphan to culture conditions enhanced the effect of SP but not of NKA.4 The selective NK1-receptor agonist produced a dose-dependent increase in cell proliferation as judged by total cell number and [3H]-thymidine uptake. No significant effect was observed with NK2-and NK3-receptor agonists. 5 These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK1-receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.