Early Changes in the Calcitonin Gene-related Peptide (CGRP) Content of Pulmonary Endocrine Cells Concomitant with Vascular Remodeling in the Hypoxic Rat

Roncalli, Massimo; Springall, David R.; Maggioni, Marco; Moradoghli-Haftvani, A.; Winter, Robert J.; Zhao, Lan; Coggi, Guido; Polak, Julia M.

doi:10.1165/ajrcmb/9.5.467

Cited by 22 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pulmonary endocrine cells, found scattered in the airway epithelium, are a major source of CGRP in rat lung [1]. They are known to respond to changes in oxygen tension [6,24,25], and suggested to contain increased levels of CGRP [7] from 4 h after exposure of rats to hypoxia [26], which is reinforced by the finding of increased CGRP concentration in lung homogenates [5]. This higher level of CGRP could represent a suppression of its release, which is supported by decreased levels of CGRP in plasma [5], and the reversal of hypoxic pulmonary vascular remodelling by administration of CGRP [27].…”

Section: Discussionmentioning

confidence: 99%

Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites

Mannan

Springall²,

Enard³

et al. 1995

Eur Respir J

Self Cite

View full text Add to dashboard Cite

Pulmonary vascular tone is regulated by many vasoactive mediators produced either locally in endothelium, airway epithelium, vascular smooth muscle or nerves, or systemically via the blood. The main effect of alveolar hypoxia is pulmonary hypertension, which is modulated by many counteracting mediators. Amongst the possible candidates is calcitonin gene-related peptide (CGRP) [1], a potent vasodilator that is also present in the sensory innervation and endocrine cells of the rat respiratory tract [1][2][3], which is known to be involved in regulating pulmonary vascular tone [2,4].In previous studies, hypoxia has been shown to cause an increase in whole lung CGRP concentrations [5], particularly in the pulmonary endocrine cells [6,7], and decreased plasma levels of the peptide in rats [5]. Release We conclude that the vasodilator effects of CGRP are endothelium-dependent and, whilst they are reduced in hypoxic lung, this is not due to reduction in receptors, thereby implicating alterations in the nitric oxide guanylyl cyclase system. Furthermore, adaptive responses in some peptide binding sites occur in hypoxia, which may be due to changes in endogenous peptide levels.Eur Respir J., 1995Respir J., , 8, 2029Respir J., -2037 of endogenous CGRP may be of importance in maintaing pulmonary equilibrium, and impaired release may, thus, be relevant to the pulmonary hypertension that is a consequence of hypoxia.Peptides elicit their effect by interacting with specific receptors on the target cell, which in turn will activate various intracellular pathways that lead to a biological response. These receptors can be identified partly by ligand binding studies and localized quantitatively by using tissue sections for the binding. CGRP binding sites are of two types, termed CGRP1 and CGRP2 [8,9].We hypothesized that changes in the amount of CGRP released will be reflected by an adaptive response shown by changes in its binding sites and, thus, its physiological effects, and have directed our study to investigate the

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites

Mannan

Springall²,

Enard³

et al. 1995

Eur Respir J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, might the products released from the cells of the system ever contribute to pulmonary pathology? It has already been described how increased numbers of neuroendocrine cells parallel the activity of myofibroblasts in PPA, suggesting a role for GRP or other pulmonary peptides in its pathogenesis, a possibility given recent support by a study of CGRP-containing neuroendocrine cells during hypoxic pulmonary vascular remodelling in the rat (Roncalli et al, 1993). Experiments in animals have suggested that these pulmonary neuroendocrine cell products might stimulate fibrogenesis (Johnson et al, 1980;Sheppard et al, 1982) and others have proposed such a role in causing the fibrosis which accompanies or results from a variety of pulmonary diseases (Aguayo et al, 1990(Aguayo et al, , 1992Johnson and Georgieff, 1989).…”

Section: Causes and Consequences Of Changes In The Systemmentioning

confidence: 91%

Pulmonary neuroendocrine cell system in pediatric and adult long disease

Gosney

1997

Microsc. Res. Tech.

View full text Add to dashboard Cite

In human lungs affected by naturally occurring pulmonary disease, the pulmonary neuroendocrine cell system, which is normally arranged in a sparse but even distribution throughout the respiratory tract, increases in size. It is likely that the stimulus for this is pulmonary injury and that its purpose is the paracrine regulation of the restoration of pulmonary tissues to their normal state, an hypothesis supported by studies of animal lungs subjected to experimental injury as well as of the development of human and animal lungs in utero. Initially, this increase involves the development of interrupted rows of neuroendocrine cells. In the later stages, however, development of more disorderly intraepithelial aggregates can occur and the small, locally invasive neuroendocrine cell lesions known as tumourlets may occasionally result. Both of these latter structures often contain secretory products not found in the neuroendocrine cells of normal human lungs, probably indicating a derangement of what appears to be a fundamentally physiological response. It is likely that, in some circumstances, this disorderly change may contribute to pulmonary disease as well as being the result of it. Microsc. Res. Tech., 37:107–113, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

“…Apparent proliferative changes have also been observed in hypoxic conditions of man and various Himalayan species of animals, and changes in the CGRP content of PNEC in experimental hypoxia in rats have been reported. Immunocytochemistry, electron microscopical and molecular biological techniques all point to an increase in the CGRP content of existing CGRP-containing cells in the airways of animals subjected to hypoxia for periods from 1 to 21 days (Roncalli et al, 1993;Springall et al, 1988) (see also below). The apparent increase in the number of CGRP-containing cells is only due to an increase in the peptide content (McBride et al, 1990) making more cells visible by immunocytochemical techniques.…”

Section: Peptides In Pnecmentioning

confidence: 99%

Quantitative microscopical methods for the identification and localisation of nerves and neuroendocrine cell markers in mammalian lung

Springall

Polak

1997

Microsc. Res. Tech.

View full text Add to dashboard Cite

The lung contains a dense innervation and a population of endocrinelike cells both of which are believed to have a role in pulmonary function and to be involved in disease processes. They contain a number of regulatory peptides that affect vascular and bronchial tone, growth and repair. They can be detected and localised by immunocytochemistry, thereby allowing investigation of the normal distribution and changes in disease processes. The application of image analysis has added greatly to the amount of information that can be obtained from such morphological studies. Data can be obtained on either the overall distribution and amount of the antigen in a tissue, thereby allowing comparisons between normal and disease states, or following experimental manipulation. Furthermore, the actual intracellular level can be assessed, which adds the previously unattained dimension of comparisons between cells. Thus the density of innervation in the specific regions of the lung tissue, either total nerves or specific peptide‐containing cells, may be estimated and used to show release of a peptide or to determine changes in the nerve density in disease. Image processing and image analysis have reduced the labour‐intensive manual input required to perform such studies. The continuing development of digital image processing and computer technology will increase the application of these methods in lung research of normal and pathological material. Microsc. Res. Tech. 37:92–100, 1997. © 1997 Wiley‐Liss, Inc.

show abstract

Early Changes in the Calcitonin Gene-related Peptide (CGRP) Content of Pulmonary Endocrine Cells Concomitant with Vascular Remodeling in the Hypoxic Rat

Cited by 22 publications

References 38 publications

Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites

Decreased endothelium-dependent pulmonary vasodilator effect of calcitonin gene-related peptide in hypoxic rats contrasts with increased binding sites

Pulmonary neuroendocrine cell system in pediatric and adult long disease

Quantitative microscopical methods for the identification and localisation of nerves and neuroendocrine cell markers in mammalian lung

Contact Info

Product

Resources

About