Inhibitory effects of calcitonin gene-related peptide on substance-P-induced superoxide production in human neutrophils

Tanabe, Takatoshi; Otani, Hitomi; Zeng, Xun-Ting; Mishima, Katsuyuki; Ogawa, Ryoukei; Inagaki, Chiyoko

doi:10.1016/s0014-2999(96)00522-5

Cited by 24 publications

(11 citation statements)

References 26 publications

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“…We have shown that sensory nerve degeneration by neonatal capsaicin treatment renders a rat sensitive to a salt load with a significant and sustained increase in blood pressure, suggesting that sensory nerves play a counterregulatory role in preventing salt-induced increases in blood pressure (33). Moreover, several studies have provided direct and indirect evidence showing that CGRP has an inhibitory effect on ROS production in tissues of deoxycorticosterone acetate-salt hypertensive rats and in neutrophils from human (3,29).Despite of the fact that oxidative stress is an important contributor to renal dysfunction in salt-sensitive hypertensive rats, the mechanisms responsible for enhanced production of oxidative stress in the kidney in salt-sensitive hypertensive rats remain to be elucidated. This study was designed to test the hypothesis that sensory nerves regulate intrarenal O 2 Ϫ ⅐ levels during high salt intake.…”

mentioning

confidence: 99%

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

Wang

Chen²,

Wang³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F(2alpha) levels increased by approximately 40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet (P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O(2)(-)*) levels in the renal cortex and medulla increased by approximately 45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). Enhanced O(2)(-)* levels in the cortex and medulla in CAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47(phox) and gp91(phox) in the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by approximately 45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats (P< 0.05). O(2)(-)* levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance (r = -0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.

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mentioning

confidence: 99%

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

Wang

Chen²,

Wang³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…On the other hand, an ameliorating effect of CGRP on the activation of endothelial cells (Harada et al 2002), adhesion molecule CD11b expression (by a cAMP-dependent mechanism; Monneret et al 2003) and the superoxide production of PMNs (Tanabe et al 1996) have been demonstrated in vitro. It is conceivable that in the course of the capsaicininduced neurogenic inflammatory response, the acute and massive release of neuropeptides produces high local tissue neuropeptide concentrations which most probably exceed the amount of mediators released by pathophysiological stimuli (e.g.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats

Hartmann

Varga

Zobolyák

et al. 2010

Naunyn-Schmied Arch Pharmacol

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We have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked by limb ischaemia-reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent mechanism. In Sprague-Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion. In further experiments, the CGRP analogue hCGRP (0.3 μg kg(-1)) or ischaemic preconditioning (2 × 10-min ischaemia/10-min reperfusion) was applied prior to the ischaemia-reperfusion insult. Ischaemic preconditioning was performed in three subgroups in which animals received the CGRP receptor antagonist CGRP(8-37) (30 μg kg(-1) h(-1)), the chemosensitive afferent nerve inactivator resiniferatoxin (3 × 15 μg kg(-1), sc), or vehicle. The effects of CGRP(8-37) and resiniferatoxin on ischaemia-reperfusion without ischaemic preconditioning were also evaluated. In the tibial periosteum of rats, intravital fluorescence microscopy and immunohistochemistry revealed significant attenuations of ischaemia-reperfusion-induced post-ischaemic leukocyte-endothelial interactions (rolling and adherence in the postcapillary venules) and tissue intracellular adhesion molecule expression following ischaemic preconditioning or hCGRP administration. Administration of CGRP(8-37) or pretreatment of animals with resiniferatoxin reversed the anti-inflammatory effects of limb ischaemic preconditioning, but failed to affect the microcirculatory consequences of ischaemia-reperfusion without ischaemic preconditioning. The results suggest that activation of the chemo- (capsaicin-) sensitive afferent nerves is involved in the mechanisms of microcirculatory anti-inflammatory protection provided by limb ischaemic preconditioning. Controlled activation of chemosensitive C-fibres or the CGRP receptors by the induction of ischaemic preconditioning or other means may furnish therapeutic benefit by ameliorating the periosteal microcirculatory consequences of tourniquet ischaemia.

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“…Substance P released by enteric neurons activates NK-1 receptors on mast cells and is a major mediator of neuron-mast cell interactions (34). After injury, substance P also exacerbates gastrointestinal inflammation by increasing superoxide production by neutrophils (35), by increasing plasma protein extravasation, and by increasing mast cell production of tumor necrosis factor-a (36), thus impairing the hyperemic response to injury (37). A translational implication of the effect on mucosal blood flow is that it would be important to administer NK-1 blockers to patients after, rather than before, each dose of radiation to avoid hyperemiaassociated radiosensitization.…”

Section: Discussionmentioning

confidence: 99%

“…This supports our findings in the capsaicin-treated rat model (3) and the observation from the present study that CGRP modulation influences postradiation neutrophil accumulation. Moreover, CGRP also suppresses tumor necrosis factor-a production (40) and counteracts substance P -induced production of reactive oxygen species by neutrophils and macrophages (35). It is also conceivable that CGRP exerts some of its protective effects by modulating mast cell function.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide and Substance P Regulate the Intestinal Radiation Response

Wang

Qiu

Kulkarni

et al. 2006

Clinical Cancer Research

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Purpose: Intestinal toxicity is important in the therapeutic use of radiation as well as in nontherapeutic radiation exposure scenarios. Enteric sensory nerves are critical for mucosal homeostasis and for an appropriate response to injury. This study assessed the role of the two major neuropeptides released by sensory nerves, calcitonin gene-related peptide (CGRP) and substance P, in the intestinal radiation response. Experimental Design: Male rats received full-length CGRP, CGRP antagonist (CGRP 8-37 ), a modified substance P peptide (GR73632), a small-molecule substance P receptor antagonist (neurokinin-1receptor antagonist, SR140333), or vehicle for 2 weeks after localized X irradiation of a 4-cm loop of small bowel. Structural, cellular, and molecular aspects of the intestinal radiation response were assessed. Results: Intestinal CGRP and substance P transcript levels increased after irradiation. Multivariate analysis showed that CGRP and SR140333 ameliorated and CGRP 8-37 and GR73632 exacerbated intestinal radiation injury. Univariate analysis revealed increased radiation injury score, bowel wall thickening, and collagen III deposition after treatment with CGRP 8-37 , whereas SR140333 ameliorated radiation injury score, loss of mucosal surface area, collagen III deposition, and mucosal inflammation. Conclusions: The two major neuropeptides released by sensory neurons, CGRP and substance P, are overexpressed after irradiation and have opposing effects during development of intestinal radiation injury. Systematic studies to assess CGRP agonists and/or neurokinin-1receptor blockers as protectors against intestinal toxicity during radiation therapy and after nontherapeutic radiation exposure are warranted.

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Inhibitory effects of calcitonin gene-related peptide on substance-P-induced superoxide production in human neutrophils

Cited by 24 publications

References 26 publications

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats

Calcitonin Gene-Related Peptide and Substance P Regulate the Intestinal Radiation Response

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