The exocrine pancreas of the rat : the relationship between DNA synthesis and secretion
The exocrine pancreas of the rat : the relationship between DNA synthesis and secretion
The secretory effects of vagal stimulation, cholinergic, adrenergic and cholecystokinin-like drugs, and their effects on DNA synthesis, in the rat pancreas were studied to investigate a possible link between secretion and cell proliferation. A reduction in the concentration of amylase in the pancreas (by up to 50% after 4 h) with carbachol (1 mg/kg i.p.), but not isoprenaline (10 mg/kg i.p.), administration was found. The effect of these drugs and vagal stimulation on the output of pancreatic secretion was also studied by cannulation of the pancreatic duct in anaesthetised rats. Cholinergic, vagal and CCK stimulation increased amylase output and secretion flow rate, whereas S-adrenoceptor stimulation only increased flow rate. A pharmacological dissociation between amylase output and flow rate is discussed. The stimulated secretion leading to a decrease in enzyme levels in the pancreas is argued to be a trigger for DNA synthesis. DNA synthesis was measured by incorporation of [6-3H]thymidine in vivo and ex vivo. The ex vivo method was by incubation of viable pieces of pancreas in physiological saline with [6-3H]thymidine. Incorporation of this DNA precursor into nucleic acid was measured by a biochemical method (involving trichloroacetic acid precipitation) and by radioautography. It was found that carbachol at the same dose as that which reduced amylase levels resulted in a 400% increase in DNA synthesis 27 h later measured biochemically; this increase was dose-dependent. B-adrenoceptor stimulation also caused an increase in C6-3H]thymidine incorporation 27 h later. However, radioautography studies showed that carbachol increased L6-3HJthymidine labelling of acinar and connective tissue cells but isoprenaline only increased connective tissue cell labelling. The possibility that it is only those treatments which cause secretion from acinar cells which cause acinar DNA synthesis is thus discussed. Also discussed are experiments indicating that part of the trophic effect may be via indirect effects, such as the release of trophic hormones or salivary gland growth factors, increased tonic vagal stimulation, and mast cell degranulation. This thesis shows that the autonomic nervous system plays a role in controlling cell division in the rat pancreas, and that the suggested link between secretion and DNA synthesis may apply to the exocrine pancreas.
University of Southampton
Carling, Robert Cecil John
1984
Carling, Robert Cecil John
Carling, Robert Cecil John
(1984)
The exocrine pancreas of the rat : the relationship between DNA synthesis and secretion.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The secretory effects of vagal stimulation, cholinergic, adrenergic and cholecystokinin-like drugs, and their effects on DNA synthesis, in the rat pancreas were studied to investigate a possible link between secretion and cell proliferation. A reduction in the concentration of amylase in the pancreas (by up to 50% after 4 h) with carbachol (1 mg/kg i.p.), but not isoprenaline (10 mg/kg i.p.), administration was found. The effect of these drugs and vagal stimulation on the output of pancreatic secretion was also studied by cannulation of the pancreatic duct in anaesthetised rats. Cholinergic, vagal and CCK stimulation increased amylase output and secretion flow rate, whereas S-adrenoceptor stimulation only increased flow rate. A pharmacological dissociation between amylase output and flow rate is discussed. The stimulated secretion leading to a decrease in enzyme levels in the pancreas is argued to be a trigger for DNA synthesis. DNA synthesis was measured by incorporation of [6-3H]thymidine in vivo and ex vivo. The ex vivo method was by incubation of viable pieces of pancreas in physiological saline with [6-3H]thymidine. Incorporation of this DNA precursor into nucleic acid was measured by a biochemical method (involving trichloroacetic acid precipitation) and by radioautography. It was found that carbachol at the same dose as that which reduced amylase levels resulted in a 400% increase in DNA synthesis 27 h later measured biochemically; this increase was dose-dependent. B-adrenoceptor stimulation also caused an increase in C6-3H]thymidine incorporation 27 h later. However, radioautography studies showed that carbachol increased L6-3HJthymidine labelling of acinar and connective tissue cells but isoprenaline only increased connective tissue cell labelling. The possibility that it is only those treatments which cause secretion from acinar cells which cause acinar DNA synthesis is thus discussed. Also discussed are experiments indicating that part of the trophic effect may be via indirect effects, such as the release of trophic hormones or salivary gland growth factors, increased tonic vagal stimulation, and mast cell degranulation. This thesis shows that the autonomic nervous system plays a role in controlling cell division in the rat pancreas, and that the suggested link between secretion and DNA synthesis may apply to the exocrine pancreas.
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Published date: 1984
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Local EPrints ID: 460397
URI: http://eprints.soton.ac.uk/id/eprint/460397
PURE UUID: 89f798ff-9f72-4129-ae62-77bac2ddfbfc
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Date deposited: 04 Jul 2022 18:21
Last modified: 04 Jul 2022 18:21
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Author:
Robert Cecil John Carling
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