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NK1 Receptor Antagonist (nk1 + receptor_antagonist)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Foot shock stress prolongs the telogen stage of the spontaneous hair cycle in a non-depilated mouse model

EXPERIMENTAL DERMATOLOGY, Issue 7 2007
Mirei Katayama
Abstract:, Background:, There is an increasing evidence to indicate that stress can influence skin disease and cutaneous functions. Previous studies have shown that stress alters the murine hair cycle; however, these studies have been carried out by using mouse models in which the hair cycle is forcibly synchronized after depilation. Objective:, To examine whether foot shock stress (FS) changes the spontaneous hair cycle in a non-depilated animal model, and to evaluate the role of mast cells and substance P (SP) in the influence of stress on the hair cycle. Methods:, Changes in the spontaneous hair cycle and the inhibitory effects of a specific SP NK1 receptor antagonist were examined in non-depilated mice during 3,4 weeks of FS. Results:, Foot shock stress prolonged the telogen stage of the hair cycle and delayed the induction of the subsequent anagen stage in the animal model. FS caused an increase in the ratio of de-granulated mast cells in the skin, an increase in the number of TUNEL-positive cells, and a decrease in the number of Ki67-positive cells. The NK1 receptor antagonist, WIN 62577, inhibited these stress responses. Conclusion:, Our results strongly support previous work, demonstrating that stress alters active hair-cycling in vivo through the action of SP. [source]

The neurokinin-1 antagonist activity of maropitant, an antiemetic drug for dogs, in a gerbil model

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007
V. DE LA PUENTE-REDONDO
Maropitant is a novel synthetic nonpeptide neurokinin type 1 (NK1) selective receptor antagonist, recently developed for use in the dog as an antiemetic. The in vivo functional activity of maropitant was investigated in the gerbil foot-tapping model, to determine the ability of maropitant to penetrate the central nervous system and inhibit foot-tapping induced by the selective NK1 agonist GR73632. In comparison with CP-122,721, a previously characterized NK1 receptor antagonist, maropitant (1 mg/kg by s.c. injection) was found to inhibit foot-tapping for significantly longer (P < 0.01). Inhibition of foot-tapping by maropitant was 100% at 2 h and approximately 50% at 8 h postdosing. The mean brain:plasma concentration ratio at 8 h post-treatment was 3.59. These data demonstrate the central functional action of maropitant as a selective and potent NK1 receptor antagonist and help to support and explain its clinical potential as a broad-spectrum antiemetic agent. [source]

Role of NK1 and NK2 receptors in mouse gastric mechanical activity

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2006
Flavia Mulè
The aim of the present study was to examine the role of NK1 and NK2 receptors in the control of mechanical activity of mouse stomach. In this view, the motor effects induced by NK1 and NK2 receptor agonists and antagonists were analyzed, measuring motility as intraluminal pressure changes in mouse-isolated stomach preparations. In parallel, immunohistochemical studies were performed to identify the location of NK1 and NK2 receptors on myenteric neurons and smooth muscle cells. Substance P (SP) induced biphasic effects: a contraction followed by relaxation; neurokinin A (NKA) and [, -Ala8]-NKA(4,10), selective agonist of NK2 receptors, evoked concentration-dependent contractions, whereas [Sar9, Met(O2)11]-SP, selective agonist of NK1 receptors, induced concentration-dependent relaxation. SR48968, NK2 receptor antagonist, did not modify the spontaneous activity and reduced the contractile effects induced by tachykinins without affecting the relaxation. SR140333, NK1 receptor antagonist, did not modify the spontaneous activity and antagonized the relaxant response to tachykinins, failing to affect the contractile effects. The relaxation to SP or to [Sar9, Met(O2)11]-SP was abolished by tetrodotoxin (TTX) and significantly reduced by N -nitro- L -arginine methyl ester (L -NAME). NK2 -immunoreactivity (NK2 -IR) was seen at the level of the smooth muscle cells of both circular and longitudinal muscle layers. NK1 -immunoreactive (NK1 -IR) neurons were seen in the myenteric ganglia and NK1/nNOS double labeling revealed that some neurons were both NK1 -IR and nNOS-IR. These results suggest that, in mouse stomach, NK1 receptors, causing relaxant responses, are present on nitrergic inhibitory myenteric neurons, whereas NK2 receptors, mediating contractile responses, are present at muscular level. British Journal of Pharmacology (2006) 147, 430,436. doi:10.1038/sj.bjp.0706645 [source]