The effect of endothelin, neuropeptide Y, calcitonin gene‐related peptide and substance P on neutrophil functions

Hafström, Ingiäld; Ringertz, Bo; Lundeberg, Thomas; Palmblad, Jan

doi:10.1111/j.1748-1716.1993.tb09565.x

Cited by 44 publications

(14 citation statements)

References 18 publications

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“…The increased adhesion was abolished by treatment with CGRP 8 -37 , indicating a selective effect of CGRP. Although one study found that CGRP (10 M) activates human neutrophils (303), a later study from a different group showed that CGRP (1 fM to 1 M) had no effect on neutrophil aggregation or chemotaxis (128). More recently, CGRP (10 M) was found to inhibit both the production of superoxide and the increase in [Ca 2ϩ ] i induced by either SP or exogenous IP 3 in neutrophils, an effect blocked by application of CGRP 8 -37 (343).…”

Section: A Cgrp: Cellular Effectsmentioning

confidence: 96%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

Grant

2004

Physiological Reviews

671

542

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This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.

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Section: A Cgrp: Cellular Effectsmentioning

confidence: 96%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

Grant

2004

Physiological Reviews

671

542

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“…Substance P, via NK-1 receptors, plays a role in regulating airway blood flow, airway smooth muscle responses, airway inflammation (18), and epithelial migration and proliferation of cells, including tracheal epithelial cells, after injury (19)(20)(21). Substance P induces superoxide production in neutrophils, is a chemotactic agent for human neutrophils, and primes neutrophils for response to other activating agents (22)(23)(24). In addition, NK-1 receptor activation has been shown to initiate nonapoptotic cell death of type I alveolar cells (25).…”

mentioning

confidence: 99%

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Oslund¹,

Hyde

Putney³

et al. 2008

Am J Respir Cell Mol Biol

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We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-29-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-29-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stresspositive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

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“…Endothelins, through activation of ET B receptors, could play a role in this type of lung injury. For instance, ET-1 primed neutrophils for superoxide generation after stimulation by f.Met-Leu-Phe peptide (45,46). Other neutrophil functions are stimulated by endothelins; ET-1 induces neutrophil chemokinesis (47) and ET-3 may have either a stimulatory or an inhibitory effect on in vitro neutrophil migration, depending on its concentration (48).…”

Section: Discussionmentioning

confidence: 99%

Association of Endothelin with Lung Hemorrhage Induced by Immune Complexes in Rats

et al. 2004

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The participation of endothelins (ETs) in a model of neutrophil-dependent lung injury induced by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigens (Arthus reaction) was investigated. Hemorrhagic lesions were evaluated by measuring the extravasations of hemoglobin in lung parenchyma. From 5 min to 24 h after the Arthus reaction (AR), endothelin (ir-ET) levels in bronchoalveolar lavage fluid (BALF) and in plasma were measured by radioimmunoassay. BALF levels of ir-ET were not different between control and AR animals for the first 90 min after the antigen challenge but increased from 2 to 24 h after induction of AR. ET levels in the plasma did not change from the respective controls over the same 24 h period. Increased ir-ET in BALF was not affected by pretreatment with L-NAME (30 mg/kg, i.v.). A PAF antagonist (BN52021; 5 and 10 mg/kg, i.v.) increased ET content in BALF and decreased the intensity of the AR. Thiorphan (2 mg/kg, i.v.) inhibited the AR-induced hemorrhagic lesions in lungs. An ET(A) receptor antagonist, BQ-123 (1 mg/kg, i.v.) potentiated, whereas the ET(B) antagonist, BQ-788 (1 mg/kg, i.v.) inhibited the lung hemorrhage. It is concluded that ETs are released during and play a role in the lung AR.

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The effect of endothelin, neuropeptide Y, calcitonin gene‐related peptide and substance P on neutrophil functions

Cited by 44 publications

References 18 publications

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

Association of Endothelin with Lung Hemorrhage Induced by Immune Complexes in Rats

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