Evidence that tachykinins relax the guinea‐pig trachea <i>via</i> nitric oxide release and by stimulation of a septide‐insensitive NK<sub>1</sub> receptor

Figini, Michela; Emanueli, Costanza; Bertrand, Claude; Javdan, Panthea; Geppetti, Pierangelo

doi:10.1111/j.1476-5381.1996.tb16725.x

Cited by 31 publications

(35 citation statements)

References 25 publications

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“…Bradykinin, endothelin-1, substance P, adenosine, and calcitonin-gene related peptide, applied to the inside of intact tracheal tubes, provoke concentration-dependent relaxations (9,93,(101)(102)(103)316). The relaxations are reversed into contractions (or contractions are markedly potentiated) by NOS inhibitors, indicating that the relaxant effect in the airways is mediated by the release of endogenous NO (9,93,(101)(102)(103)316).…”

Section: In Vitro Studiesmentioning

confidence: 93%

“…The relaxations are reversed into contractions (or contractions are markedly potentiated) by NOS inhibitors, indicating that the relaxant effect in the airways is mediated by the release of endogenous NO (9,93,(101)(102)(103)316). This effect was mimicked by removal of airway epithelium (111), suggesting that airway epithelium releases NO, which counteracts smooth muscle contraction induced by different spasmogens (9,93,(101)(102)(103)316). These striking results demonstrate the functional importance of epithelium in airway reactivity, not merely considered as a physical protective barrier between spasmogens and smooth muscle but as a modulator of bronchomotor tone via the release of relaxant substances (so-called epithelium-derived relaxing factors).…”

Section: In Vitro Studiesmentioning

confidence: 99%

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Nitric Oxide in Health and Disease of the Respiratory System

Ricciardolo¹,

Sterk²,

Gaston³

et al. 2004

Physiological Reviews

773

649

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During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.

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Section: In Vitro Studiesmentioning

confidence: 93%

Section: In Vitro Studiesmentioning

confidence: 99%

Nitric Oxide in Health and Disease of the Respiratory System

Ricciardolo¹,

Sterk²,

Gaston³

et al. 2004

Physiological Reviews

773

649

View full text Add to dashboard Cite

show abstract

“…Substance P is a major mediator of neurogenic inflammation in several tissues including skin (20,21), cardiovascular tissue (6, 9, 25), cephalic structures (13,17,26), respiratory tract (7,15,27), genitourinary tract (23,30), and gastrointestinal tract (12,16,25,32). NKA has also been shown to play an important role in neurogenic inflammation in several conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Substance P is released from nerve endings in many tissues. Subsequent to its release, substance P binds primarily, but not exclusively, to NK1 receptors on the surface of effector cells and, in addition to being a mediator of pain, acts as a proinflammatory mediator in many inflammatory states (20) including asthma (15,27), immune-complex-mediated lung injury (7), experimental arthritis (40), and inflammatory bowel disease (41). NKA binds primarily to NK2 receptors.…”

mentioning

confidence: 99%

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Bhatia

Slavin

Cao

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.

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“…TKs in general, and in particular the NK-1 receptor agonist SP, mediate a variety of inflammatory processes including asthma (8,21), inflammatory bowel disease (38), arthritis (36), and also pancreatitis (3). Information is lacking on the exact events during pancreatitis.…”

mentioning

confidence: 99%

Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats

Broccardo

Linari²,

Agostini³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Activation of neurokinin (NK)-1 receptors but not of NK-3 stimulates amylase release from isolated pancreatic acini of the rat. Immunofluorescence studies show that NK-1 receptors are more strongly expressed than NK-3 receptors on pancreatic acinar cells under basal conditions. No studies have examined the expression of the two NK receptor populations in pancreatic acini during pancreatitis in rats. We therefore investigated the relationships between expression of these two tachykinin receptors and experimental acute pancreatitis induced by stimulating pancreatic amylase with caerulein (CK) in rats. Hyperstimulation of the pancreas by CK caused an increase in plasma amylase and pancreatic water content and resulted in morphological evidence of cytoplasmic vacuolization. Immunofluorescence analysis revealed a similar percentage of NK-1 receptor antibody immunoreactive acinar cells in rats with pancreatitis and in normal rat tissue but a larger percentage of NK-3 receptor immunoreactive cells in acute pancreatitis than in normal pancreas. Western blot analysis of NK-1 and NK-3 receptor protein levels after CK-induced pancreatitis showed no change in NK-1 receptors but a stronger increase in NK-3 receptor expression in pancreatic acini compared with normal rats thus confirming the immunofluorescence data. These new findings support previous evidence that substance P-mediated functions within the pancreas go beyond sensory signal transduction contributing to neurogenic inflammation, and they suggest that substance P plays a role in regulating pancreatic exocrine secretion via acinar NK-1 receptors. The significant increase in NK-3 receptors during pancreatic stimulation suggests that NK-3 receptors also intervene in the pathogenesis of mild acute pancreatitis in rats. isolated pancreatic acini; tachykinin receptor distribution; immunofluorescence; Western blot analysis THE NEUROPEPTIDES substance P (SP), neurokinin (NK)-A, and NK-B are primary mammalian tachykinins (TKs) involved in a wide-ranging control of peripheral and central functional activities. Each TK preferentially binds to a specific cell surface receptor subtype belonging to the superfamily of G proteincoupled receptors: SP binds to the NK-1 receptor, NK-A to the NK-2 receptor, and NK-B to the NK-3 receptor. TKs and their receptors are diffusely distributed in the mammalian gastrointestinal tract where they mediate motor, secretory, and circulatory responses (10).To date, few reports exist on the role of the TKs in regulating exocrine pancreatic secretion. TKs acting on NK-1 and NK-2 receptors have been reported to stimulate in vitro pancreatic amylase secretion (12-14, 16, 20, 33), and NK-1 and NK-2 receptors have been detected in the pancreatic acinar cells of guinea pig and mouse (6,11,29,30,32). No information is available on whether acinar cells in the pancreas of these and other animal species express the NK-3 receptor, and little is known on the effects of NK-3 receptor agonists on pancreatic exocrine secretion (7,12,18,20,33). In our recent stud...

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Evidence that tachykinins relax the guinea‐pig trachea via nitric oxide release and by stimulation of a septide‐insensitive NK₁ receptor

Cited by 31 publications

References 25 publications

Nitric Oxide in Health and Disease of the Respiratory System

Nitric Oxide in Health and Disease of the Respiratory System

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats

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Evidence that tachykinins relax the guinea‐pig trachea via nitric oxide release and by stimulation of a septide‐insensitive NK1 receptor

Cited by 31 publications

References 25 publications

Nitric Oxide in Health and Disease of the Respiratory System

Nitric Oxide in Health and Disease of the Respiratory System

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats

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Evidence that tachykinins relax the guinea‐pig trachea via nitric oxide release and by stimulation of a septide‐insensitive NK₁ receptor