The tachykinin NK1 receptor. Part II: Distribution and pathophysiological roles

Quartara, Laura; Maggi, Carlo Alberto

doi:10.1016/s0143-4179(98)90015-4

Cited by 261 publications

(164 citation statements)

References 516 publications

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“…The NK-1 receptor, the preferred receptor of SP, mediates a variety of physiological and pathophysiological responses (22,23,43). Although previous studies have confirmed that SP enhances corneal epithelial migration when combined with IGF-1 or EGF (41,44,45), the exact mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

et al. 2014

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Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose–treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied by attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt, epidermal growth factor receptor (EGFR), and Sirt1 activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted epithelial wound healing, recovery of corneal sensation, improvement of mitochondrial function, and reactivation of Akt, EGFR, and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose–treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a neurokinin-1 (NK-1) receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 receptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.

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Section: Discussionmentioning

confidence: 99%

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

et al. 2014

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“…Peripheral blood MO were isolated from heparinized venous blood (30-40 ml) by standard techniques of dextran sedimentation (dextran T-500; Pharmacia, UK) and Ficoll-Paque (density = 1.077 g/cm 3 ; Pharmacia) gradient centrifugation (400×g, 30 min) and recovered by thin suction at the interface. Cells were washed twice with balanced phosphate-buffered saline (PBS,) (pH 7.4; Sigma, UK) and resuspended at 1-2×10 7 /ml in RPMI 1640 medium, supplemented with 5% heat-inactivated fetal calf serum (Sigma), 2 mM glutamine (Sigma), 50 µg/ml streptomicin and 5 U/ml penicillin (Sigma).…”

Section: Isolation Of Peripheral Blood Monocytesmentioning

confidence: 99%

“…[1][2][3] The undecapeptide SP, which is synthesized in primary afferent neurons and released from the terminals in response to different stimuli, is known to largely contribute to the local control of the inflammatory and immune responses. It stimulates lymphocyte proliferation and interacts with specific receptors on human T lymphocytes and cultured IM-9 lymphoblasts; degranulates mast cells and induces TNF-α mRNA and TNF-α release from human skin mast cells; modulates human neutrophil activity (by stimulating phagocytosis and Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers priming PMN for an enhanced respiratory burst); induces eosinophil activation and fibroblast proliferation; acts synergistically with insulin-like growth factor-1 to enhance corneal epithelial migration; and stimulates guinea-pig peritoneal macrophages as well as rodent and human alveolar macrophages.…”

Section: Introductionmentioning

confidence: 99%

Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers

et al. 2000

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Summary Three types of tachykinin receptors, NK 1 , NK 2 and NK 3 , have been described to preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) respectively. Experimental evidence indicates that SP and NKA modulate the activity of inflammatory and immune cells, including mononuclear ones, and points to their involvement in lung pathophysiology. We previously reported that NK 1 and NK 2 receptors are present on monocytes (MO) isolated from healthy donors or rheumatoid patients -a greater sensitivity to NK 2 receptor stimulation was observed in the latter condition. This study evaluated the effects of SP and NKA, as well as NK 1 and NK 2 selective agonists and antagonists, on MO obtained from healthy volunteers, healthy smokers or patients with interstitial lung diseases (e.g. sarcoidosis and idiopathic pulmonary fibrosis). Superoxide anion (O 2 -) production was chosen as a parameter of cell activation. SP and NKA dose-dependently evoked O 2 -production from MO in all the conditions evaluated, their effects being competitively antagonized by selective antagonists (CP 96 345 and MEN 10 627, respectively). When selective NK 1 and NK 2 agonists were used, [Sar 9 Met(O 2 ) 11 ]SP, a selective NK 1 agonist, induced a more than doubled O 2 production in MO obtained from patients with interstitial lung diseases as compared to healthy volunteers, whereas MO isolated from healthy volunteers were more sensitive to NK 2 receptor stimulation.

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“…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).…”

mentioning

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.

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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...

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The tachykinin NK1 receptor. Part II: Distribution and pathophysiological roles

Cited by 261 publications

References 516 publications

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

Substance P Promotes Diabetic Corneal Epithelial Wound Healing Through Molecular Mechanisms Mediated via the Neurokinin-1 Receptor

Tachykinin activation of human monocytes from patients with interstitial lung disease, healthy smokers or healthy volunteers

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

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