Differences in the distribution and characteristics of tachykinin NK<sub>1</sub> binding sites between human and guinea pig lung

Walsh, David A.; Salmon, M; Featherstone, Roland L.; Wharton, John; Church, Martin K.; Polak, Julia M.

doi:10.1111/j.1476-5381.1994.tb17154.x

Cited by 17 publications

(6 citation statements)

References 34 publications

(53 reference statements)

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“…Although previous studies of NK-1 receptor localization in the normoxic lung have generated conflicting results, our findings are consistent with previous work suggesting that very few detectable NK-1 receptors are present in the normal distal lung in rats, guinea pigs, or humans (8,17,29).…”

Section: Discussionsupporting

confidence: 91%

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Zee

Schomberg²,

Carpenter³

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Subacute exposure to moderate hypoxia can promote pulmonary edema formation. The tachykinins, a family of proinflammatory neuropeptides, have been implicated in the pathogenesis of pulmonary edema in some settings, including the pulmonary vascular leak associated with exposure to hypoxia. The effects of hypoxia on tachykinin receptor and peptide expression in the lung, however, remain poorly understood. We hypothesized that subacute exposure to moderate hypoxia increases lung neurokinin-1 (NK-1) receptor expression as well as lung substance P levels. We tested this hypothesis by exposing weanling Sprague-Dawley rats to hypobaric hypoxia (barometric pressure 0.5 atm) for 0, 24, 48, or 72 h. Hypoxia led to time-dependent increases in lung NK-1 receptor mRNA expression and lung NK-1 receptor protein levels at 48 and 72 h of exposure (P Ͻ 0.05). Immunohistochemistry and in situ NK-1 receptor labeling with substance Pconjugated fluorescent nanocrystals demonstrated that hypoxia increased NK-1 expression primarily in the pulmonary microvasculature and in alveolar macrophages. Hypoxia also led to increases in lung substance P levels by 48 and 72 h (P Ͻ 0.05) but led to a decrease in preprotachykinin mRNA levels (P Ͻ 0.05). We conclude that subacute exposure to moderate hypoxia upregulates lung NK-1 receptor expression and lung substance P peptide levels primarily in the lung microvasculature. We speculate that this effect may contribute to the formation of pulmonary edema in the setting of regional or environmental hypoxia. tachykinin; pulmonary edema; acute respiratory distress syndrome ACUTE LUNG INJURY and acute respiratory distress syndrome (ARDS) are clinical syndromes associated with significant morbidity and mortality in humans. The hallmarks of these syndromes are increased pulmonary capillary permeability, pulmonary edema formation, and profound hypoxemia (22). The precise mechanisms that lead to this pulmonary vascular leak remain uncertain (3, 21, 27), although many inflammatory and vasoactive substances have been implicated.Among the mediators implicated in the development of pulmonary edema are the tachykinins. These molecules, a part of the nonadrenergic, noncholinergic nervous system, are a family of peptides that are expressed in the lung in and around the pulmonary vasculature as well as in sensory nerves located primarily near the airways. Substance P, the tachykinin peptide most highly expressed in the lung, exerts its effects primarily through the neurokinin-1 (NK-1) receptor. This ligand-receptor pair mediates neurogenic inflammation in the airways via cytokines including IL-1, 20). In addition, substance P levels are markedly elevated in pulmonary edema fluid from ARDS patients (6), and the NK-1 receptor has been implicated in the pathophysiology of lung injury associated with pancreatitis (13), smoke inhalation (30), and viral infections (23) including respiratory syncytial virus (11).Previous work has also suggested that the tachykinin system may be altered in response to hypoxia. In particular,...

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Section: Discussionsupporting

confidence: 91%

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Zee

Schomberg²,

Carpenter³

2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Nerves containing tachykinins and tachykininbinding sites exist in the esophagus as well as in the airways (18,40). Because the esophageal and pulmonary systems share a similar embryological origin, the foregut, it would not be surprising if they also shared a common nerve pathway.…”

mentioning

confidence: 99%

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

Hamamoto¹,

Kohrogi²,

Kawano

et al. 1997

Journal of Applied Physiology

113

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To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

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“…Autoradiographic studies have detected binding sites for substance P in airway smooth muscle in the rabbit ASTHMA MEDIATORS (Black et al 1990). However, little, if any, binding for substance P was detected in airway smooth muscle in man (Goldie 1990;Walsh et al 1994) even though binding sites for substance P have been reported in one study of human airway smooth muscle (Carstairs & Barnes 1986). Whether methodological differences can account for these discrepancies is unclear but would seem unlikely, given that substance P binding sites were clearly detected in the microvasculature and submucosal glands of humans (Goldie 1990;Walsh et al 1994).…”

Section: Sensory Neuropeptidesmentioning

confidence: 97%

“…However, little, if any, binding for substance P was detected in airway smooth muscle in man (Goldie 1990;Walsh et al 1994) even though binding sites for substance P have been reported in one study of human airway smooth muscle (Carstairs & Barnes 1986). Whether methodological differences can account for these discrepancies is unclear but would seem unlikely, given that substance P binding sites were clearly detected in the microvasculature and submucosal glands of humans (Goldie 1990;Walsh et al 1994). Functional studies have revealed that tachykinins contract human isolated bronchi via NK 2 -receptors (Naline et al 1989;Advenier et al 1992).…”

Section: Sensory Neuropeptidesmentioning

confidence: 97%

Asthma Mediators: Current Views

Spina

2000

Journal of Pharmacy and Pharmacology

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Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung

Abstract: The distribution and characteristics of tachykinin NK, binding

Cited by 17 publications

References 34 publications

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

Asthma Mediators: Current Views

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Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung

Abstract: The distribution and characteristics of tachykinin NK, binding

Cited by 17 publications

References 34 publications

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Hypoxia upregulates lung microvascular neurokinin-1 receptor expression

Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

Asthma Mediators: Current Views

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Differences in the distribution and characteristics of tachykinin NK₁ binding sites between human and guinea pig lung