The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. I. Submaxillary Gland Morphology and Ultrastructure

Martínez, Vicente; Adelstein, Edward H.; Quissel, D; Gj, Barbero

doi:10.1203/00006450-197505000-00001

Cited by 70 publications

(34 citation statements)

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“…In addition, the response to stimulation with pilocarpine is enhanced in the treated animals, in terms of the secretion of these organic components, when compared to that of untreated controls. These observations suggest that, as was previously observed in th& submaxillary salivary gland (18,19), the drug treatment induces a hypersecretory state in the airways, involving an increased release of mucous glycoproteins. It appears, therefore, that the reserpine-treated animal model develops a fairly generalized exocrine gland disturbance, with characteristics that resemble those of CF patients (7).…”

Section: Discussionsupporting

confidence: 62%

“…An animal model for CF developed by the chronic administration of reserpine to rats shows not only morphologic and secretory changes in the salivary glands (16,17,18,19) and pancreas (20), but also alterations in the protein content of pulmonary lavage fluids, involving a significant increase in the total protein content and in the absolute and relative amounts of a low molecular weight glycoprotein, which were also observed in lung lavage samples from patients with CF (28).…”

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confidence: 97%

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The Chronically Reserpinized Rat as an Animal Model for Cystic Fibrosis: I. Acute Effect of Isoproterenol and Pilocarpine upon Pulmonary Lavage Fluid

et al. 1979

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SummaryLung lavage samples from rats treated in a chronic fashion with reserpine had mean increases of 133, 170, and 120% in the total protein, lipid, and carbohydrate contents, respectively, when compared with those of untreated control animals, when these values were expressed in terms of body weight. An acute single ip injection of the /I-adrenergic agent isoproterenol(10 mg) increased the glycoprotein content of pulmonary lavage fluid from control rats approximately 15-19%, but only 9-10% in those from reserpine tieated rats. By contrast, pilocarpine (10 mg), administered in the same manner, caused a 15% increase in the total protein, carbohydrate, and lipid content of lavage samples from control rats and increased these same constituents in the lavage samples of reserpine treated rats 98, 102, and 80%, respectively. The increased total carbohydrate content in the lavage samples of the treated animals was not associated with changes in the percent distribution of neutral sugars, amino sugars, or sialic acid. The. ratio of these various sugar components did not change in the lavage samples of control or reserpine treated rats upon stimulation with either pilocarpine or isoproterenol. The increased total lipid content fround in the lavage samples from the treated rats probably results from an increase in phospholipids. A decrease in phospholipid content qccurred in the lavage samples of reserpine treated rats upon stimulation, while the opposite was observed in those of control animals. Chronic treatment of rats with reserpine. thus, appears to induce an enhanced production of glycoproieins in the airwavs and to interfere with phospholi~id metabolism in m m -the lung. In addition, the drug treatment enhances the secretory response to pilocarpine in comparison with the responses of control animals. The enhanced response or hypersecretion of glycoproteins is a quantitative one and does not seem to involve alterations in the ratios or distribution of the various sugar components. This disturbance in the secretory function of the respiratory tract, a target organ which is prominently involved in cystic fibrosis (CF) together with alterations in other exocrine glands which resemble those of CF patients, makes the reserpine treated rat a useful model for the further study of possible pathogenetic mechanisms in CF.Speculation enhanced in the treated animals when compared to that of untreated control rats. It therefore appears that chronic reserpine administration causes a hyperse&tion of glycoproteins and changes in lipid metabolism in the respiratorv tract of the rat and -that, in conjunction with previous findings in other exocrine glands, these effects on lung function make the reserpine treated rat a useful tool for the study of the pathologic disturbance seen in the major exocrine glands affected in CF.An animal model for CF developed by the chronic administration of reserpine to rats shows not only morphologic and secretory changes in the salivary glands (16,17,18,19) and pancreas (20), but also alterations ...

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Section: Discussionsupporting

confidence: 62%

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confidence: 97%

The Chronically Reserpinized Rat as an Animal Model for Cystic Fibrosis: I. Acute Effect of Isoproterenol and Pilocarpine upon Pulmonary Lavage Fluid

et al. 1979

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“…In view of our previous observations in the submaxillary gland (11,12) and in the pulmonary secretions (16) of the reserpinetreated rat, the similarity between the disturbances in the pancreatic secretory response of the CF patient (5) and of the treated animal lends support to the view that it constitutes a useful animal model for the human disease. The relevance of this model, in contrast to the isoproterenol-treated rat (8), resides in the prominent involvement of several exocrine tissues that are affected in CF and in the importance that the marked effects of reserpine on the secretory capacity of these target tissues may have in elucidating possible pathogenetic mechanisms in CF.…”

Section: Pancreas Weights and Compositionmentioning

confidence: 70%

“…In the first of these models, changes in the excretion of monovalent ions and of basic proteins from the rat parotid gland were observed after chronic administration of that administration of reserpine for several days induces morphologic and secretory changes in the rat submaxillary gland which resemble those of cystic fibrosis (CF) (11,12). In addition, we have shown that this procedure increases the secretion of total protein and of a specific type of glycoprotein from the lungs of the treated animals, in a manner that parallels the abnormalities seen in lavage specimens from C F patients (16).…”

Section: Speculationmentioning

confidence: 99%

The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. VII. Alterations in the Secretory Response to Cholecystokinin and to Secretin from the Pancreas in Vivo

Perlmutter

Martinez

et al. 1978

Pediatr Res

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Summary .isoproterenol (8). In the second model, we have demonstratedThe chronically reserpinized rat has been proposed as an animal model for cystic fibrosis on the basis of morphologic and secretory alterations in the submaxillary gland and of abnormalities in pulmonary secretions. In this investigation, the volume and composition of pancreatic juice from reserpine treated rats (0.5 mg/kg/day) have been compared to those of untreated controls after stimulation with purified cholecystokinin (0.1 pg/ kg body wt) and with crude and purified preparations of secretin (6p/100 g body wt) infused iv for 30-min periods. The results demonstrate that the treated animals secreted a significantly lower volume of pancreatic juice after stimulation with these secretagogues. Fldw rates were also significantly reduced after stimulation with cholecvstokinin and crude secretin. Protein and amylase outputs in response to cholecystokinin were smaller than in control animals after unrestricted feedings, but greater after a 24-hr fast. Total bicarbonate output was also reduced after stimulation with either crude or purified secretin and the normal excretion patterns for bicarbonate and chloride were either absent or reversed in the secretin-stimulated pancreatic juice of the treated animals. Whole pancreas homogenates from the treated animals showed significant increases in Ca++ and protein content. These results indicate that chronic administration of reserpine alters the secretion of water, protein, and bicarbonate from the rat pancreas and that it affects several of the exocrine glands involved in cystic fibrosis. These findings lend support to the concept of an animal model for the human disease. SpeculationThe chronic administration of reserpine to rats has been shown to induce alterations in salivary and pulmonary secretions which resemble those seen in patients with cystic fibrosis. The concept of an animal model has been proposed on the basis of these observations. The pancreas is another exocrine gland prominently involved in cystic fibrosis and if it can be demonstrated that reserpine administration also induces alterations in pancreatic secretion, the concept of the animal model would be strengthened considerably.The generalized exocrine gland dysfunction which is characteristic of cystic fibrosis (3) has been partially reproduced in experimental animal models induced by treating rats in a chronic fashion with certain drugs that influence the level of autonomic input into these tissues. In the first of these models, changes in the excretion of monovalent ions and of basic proteins from the rat parotid gland were observed after chronic administration of that administration of reserpine for several days induces morphologic and secretory changes in the rat submaxillary gland which resemble those of cystic fibrosis (CF) (11,12). In addition, we have shown that this procedure increases the secretion of total protein and of a specific type of glycoprotein from the lungs of the treated animals, in a manner that parallels the abn...

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“…One such model is the chronically reserpinized rat. Rats treated for several days with reserpine develop morphologic and secretory changes in the submaxillary gland (9,11) and in the pancreas (6,16) which resemble those present in CF patients. The Na+ transport inhibitory factor, present in the saliva of CF patients (7) has been demonstrated in the saliva of reserpinized rats as well (13).…”

Section: Speculationmentioning

confidence: 99%

Pancreatic Function in the Reserpinized Rabbit—a Model for Cystic Fibrosis. I. Effect of Secretin

1982

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Summaryby CF, ~ancreatic secretions have not been as extensively studiedPancreatic juice was collected from rabbits treated with reserpine and from untreated controls. The volume of pancreatic juice secreted, flow rate and the bicarbonate output were all significantly reduced in the treated animals during both spontaneous flow and during secretin-stimulated flow. On the other hand, the total protein concentration, the amylase activity and the calcium concentration of the pancreatic juice were all significantly elevated in the treated animals. The elevation in the total protein concentration appeared to be due to both increased amounts of protein and decreased amounts of water. Of particular interest was that secretin stimulation caused the same % increase in the flow rate and output of pancreatic juice in both control and reserpine treated rabbits. he method-by which fluid is secreted by-the treated animal, therefore, appeared to be depressed at all times and under all conditions. Decreased volumes of pancreatic juice, a decreased bicarbonate output and increased concentrations of protein and calcium are found in this model and are consistent with clinical findings present in the pancreatic secretions obtained from individuals with cystic fibrosis. Therefore, the similarities between secretions of the reserpine treated rabbit and those observed in the cystic fibrosis patient support its use as an experimental model for investigating the abnormal pancreatic secretions in this disease. SpeculationRabbits treated with reserpine for 7 days secrete smaller volumes of pancreatic juice at lower rates of flow during both spontaneous and secretin-stimulated conditions. This juice contains elevated levels of total protein, enzymes, calcium and smaller amounts of bicarbonate. Because these alterations are common in patients with CF, the reserpine-treated rabbit appears to be a good model to investigate the perturbations taking place in the pancreas during the course of this disease.The study of cystic fibrosis (CF) has been hampered by the lack of an equivalent disease in a lower species. For this reason attempts have been made to pharmacologically perturb the exocrine secretions of an experimental animal to the point where they resemble what is seen in this disease (8,10). One such model is the chronically reserpinized rat. Rats treated for several days with reserpine develop morphologic and secretory changes in the submaxillary gland (9, 11) and in the pancreas (6, 16) which resemble those present in CF patients. The Na+ transport inhibitory factor, present in the saliva of CF patients (7) has been demonstrated in the saliva of reserpinized rats as well (13). In addition, this treatment increases the pulmonary secretion of phospholipids (14), total protein (21) and of a specific type of glycoprotein which is also present in lung lavages of CF patients (21). These alterations seem to indicate that reserpinization creates a generalized exocrine gland dysfunction resulting in a fairly complete animal model with which this d...

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The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. I. Submaxillary Gland Morphology and Ultrastructure

Cited by 70 publications

References 6 publications

The Chronically Reserpinized Rat as an Animal Model for Cystic Fibrosis: I. Acute Effect of Isoproterenol and Pilocarpine upon Pulmonary Lavage Fluid

The Chronically Reserpinized Rat as an Animal Model for Cystic Fibrosis: I. Acute Effect of Isoproterenol and Pilocarpine upon Pulmonary Lavage Fluid

The Chronically Reserpinized Rat as a Possible Model for Cystic Fibrosis. VII. Alterations in the Secretory Response to Cholecystokinin and to Secretin from the Pancreas in Vivo

Pancreatic Function in the Reserpinized Rabbit—a Model for Cystic Fibrosis. I. Effect of Secretin

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