The mammalian tachykinin receptors

Maggi, Carlo Alberto

doi:10.1016/0306-3623(94)00292-u

Cited by 465 publications

(319 citation statements)

References 220 publications

Supporting

Mentioning

307

Contrasting

Unclassified

Order By: Relevance

“…Its primary ligand is SP, but other members of the tachykinin family can also activate NK-1R, including hemokinin-1 at equimolar affinity to SP (29,30), and neurokinins A and B at lower affinity (31). There are several potential sources of SP that could activate tr-NK-1R in CAC.…”

Section: Discussionmentioning

confidence: 99%

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer

Gillespie¹,

Leeman²,

Watts³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Patients with chronic ulcerative colitis (UC) are at high risk for developing colorectal cancer. In this study, archival formalin-fixed paraffin-embedded colonic tissue from patients with UC who developed carcinoma (CA) or high-grade dysplasia (HGD) was examined for changes in expression of the proinflammatory and mitogenic neurokinin-1 receptor (NK-1R). Laser capture microscopy was used to microdissect epithelia from areas of colons that showed histologic evidence of CA, HGD, and epithelia that were not dysplastic or cancerous but did contain evidence of prior inflammation (quiescent colitis). mRNA was extracted from the dissected tissue, and PCR array analysis was performed on extracted mRNA. Two antibodies were necessary to separately estimate the protein levels of the truncated (tr-NK-1R) and full-length (fl-NK-1R) receptors by immunohistochemistry. mRNA expression of tr-NK-1R increased 14-fold (P = 0.02) when comparing the HGD and CA groups. In contrast, the fl-NK-1R transcript showed no significant differences among groups. The protein levels of the total NK-1R increased by 40% (P = 0.02) in HGD and 80% (P = 0.0007) in CA compared with quiescent colitis. There were no significant changes in protein levels of the fl-NK-1R. We conclude that the increase in total NK-1R protein in HGD and CA is attributable to an increase in tr-NK-1R, suggesting there may be a functional role for tr-NK-1R in malignant transformation in colitis-associated cancer. The tr-NK-1R could prove useful as a diagnostic marker to identify patients at risk for neoplasia and may serve as a useful therapeutic target in the treatment of colitisassociated cancer.colon cancer | receptor splice variants | substance P | IBD C hronic inflammation is associated with a higher rate of cancer development in various organs (1). More specifically, patients with ulcerative colitis (UC) are at high risk for developing colorectal cancer (2); both extent and duration of intestinal inflammation further increase risk (3, 4). These associations suggest that chronic intestinal inflammation is a causative factor in carcinogenesis in patients with UC, and that there is a causal link between chronic inflammation and increased risk of cancer. These observations raise the question of the signaling pathways by which long-standing inflammation might underlie the development of cancer.Substance P (SP) is a proinflammatory neuropeptide described by von Euler and Gaddum (5) and later isolated and characterized by Chang and Leeman (6). SP is synthesized by a variety of cells, most notably neurons and inflammatory cells such as macrophages (7). SP's primary receptor, the neurokinin-1 receptor (NK-1R), can mediate a variety of physiologic and pathophysiologic responses, including cell proliferation, migration, and inflammation (8). The NK-1R has been identified in epithelial cells in rodent models of colonic inflammation (9, 10) and in patients with UC as well as Crohn disease (11)(12)(13)(14). However, not all of these studies are in agreement regarding epithelial NK-1R e...

show abstract

Section: Discussionmentioning

confidence: 99%

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer

Gillespie¹,

Leeman²,

Watts³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Their biological actions are mediated via the activation of three receptors: the tachykinin NK 1 , tachykinin NK 2 , and tachykinin NK 3 receptors (Regoli et al, 1994). While tachykinin NK 1 and tachykinin NK 3 receptors are widely distributed in the CNS, the tachykinin NK 2 receptor is found centrally with considerably lower levels (Maggi, 1995;Otsuka and Yoshioka, 1993). All three types of tachykinin receptors are located in brain areas implicated in the control of fear and anxiety, such as the hypothalamus, amygdala, hippocampus, and periaqueductal gray matter (Otsuka and Yoshioka, 1993).…”

Section: Effects Of Tachykinin Receptor Ligands In the Mouse Defense mentioning

confidence: 99%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2003

European Journal of Pharmacology

258

159

View full text Add to dashboard Cite

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

show abstract

“…These multiple tachykinin receptors have been identified in peripheral organs using bioassay and radioligand binding methods, and confirmed through the development of selective antagonists and the molecular cloning of the three receptor proteins (Maggi 1995). In view of the fact that NKA preferentially binds to NK-2 receptors, it is likely that this receptor subtype is involved in the neuroendocrine effects of NKA.…”

Section: Introductionmentioning

confidence: 94%

The hormonal status modulates the effect of neurokinin A on prolactin secretion in female rats

Pisera

Theas²,

Laurentiis³

et al. 1998

Journal of Endocrinology

View full text Add to dashboard Cite

We have previously reported that neurokinin A (NKA), a tachykinin closely related to substance P, increases the release of prolactin (PRL) from the anterior pituitary gland of male rats, but not from pituitaries of ovariectomized (OVX) female rats. In this study, we evaluated the influence of estrogens in the action of NKA on PRL secretion in female rats. NKA stimulated the in vitro release of PRL from pituitary glands of OVX-chronically estrogenized rats, and of proestrus and estrus rats, but had no effect in anterior pituitaries of diestrus rats. In addition, we observed that cultured anterior pituitary cells of OVX rats responded to NKA only when they were incubated for 3 days in the presence of estradiol 10 9 M. This effect was blocked by L-659,877, an NK-2 receptor antagonist. We also studied the action of NKA on PRL release during lactation. The response of anterior pituitary cells to NKA was variable over this period. The maximal sensitivity to NKA was observed at day 10 of lactation. Furthermore, the blockade of endogenous NKA by the administration of an anti-NKA serum to lactating rats reduced the PRL surge induced by the suckling stimulus. These results show that the responsiveness of the anterior pituitary gland of female rats to NKA is modulated by the endocrine environment, and suggest that NKA may participate in the control of PRL secretion during the estrus cycle and lactation.

show abstract

The mammalian tachykinin receptors

Cited by 465 publications

References 220 publications

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

The hormonal status modulates the effect of neurokinin A on prolactin secretion in female rats

Contact Info

Product

Resources

About