sincalide and Starvation

Cholecystokinin (CCK) and its analogues are known to exert trophic effects on the exocrine pancreas, whereas at high doses, they produce pancreatic injury. This study was carried out to study the effect of starvation on the dose-dependent pancreatotrophic effect of CCK-8 in rats. Normal or fasted rats were treated with CCK-8 doses ranging from 0.5 to 32 and 0.5 to 8 micrograms kg-1, respectively, twice daily for 5 days. Pancreatic size, protein, DNA, secretory enzyme and trypsin inhibitor (PSTI) contents as well as histology were examined. In normal rats, CCK-8 increased the pancreatic content of protein, amylase, serine proteases and PSTI with maximum values between doses of 2 and 16 micrograms kg-1. The dose of 32 micrograms kg-1, however, yielded less trophic responses. Given to fasted rats, CCK-8 increased the weight as well as protein and secretory enzyme contents of the pancreas with maximum values between doses of 1 and 4 micrograms kg-1. The first dose supramaximum for the trophic responses was as low as 8 micrograms kg-1. Histology revealed necroinflammatory damage (acinar cell vacuolization, focal cell necrosis) in the exocrine pancreas at supramaximum doses of CCK-8 in both groups. Cell necroses and vacuolization were less but present even at doses optimum for trophism and exhibited dependence on both the dose of CCK-8 and nutrition. In either the normal or fasted animals, the periinsular acini were relatively less affected by the toxic effects of CCK-8 than the teleinsular ones. The results indicate that starvation makes the exocrine pancreas more sensitive to necroinflammatory effects of CCK-8. The relative protection seen in periinsular acini suggests a modulatory influence of islet hormones on development of CCK-induced acinar cell injury.

Topics: Animals; Body Water; DNA; Dose-Response Relationship, Drug; Male; Organ Size; Pancreas; Pancreatitis; Protein Biosynthesis; Rats; Rats, Wistar; Sincalide; Starvation

The present study was performed to characterize a direct influence of cyclosporine A (CsA) on exocrine pancreatic enzyme secretion. CsA inhibited dose-dependently amylase release from isolated rat pancreatic acini in response to carbachol or cholecystokinin octapeptide (CCK-8). A significant reduction in amylase release by 17% was observed at 0.2 mumol/l CsA (p < 0.001) when compared to controls. At 0.2 mmol/l, CsA reduced amylase release in response to both secretagogues by maximally 45%, whereas basal secretion was not affected. CsA had no influence on CCK-8-stimulated increase in intracellular Ca2+ concentrations or amylase release in response to the Ca2+ ionophore A 23187. In contrast, the dose-response curve for amylase secretion induced by the phorbol ester phorbolmyristate-13-acetate was shifted to the right without a reduction of the maximal secretory response. Unexpectedly, vasoactive-intestinal-polypeptide- and secretin-stimulated acinar secretion was not diminished by CsA. In isolated pancreatic lobules exposed to 0.1 mmol/l CsA, amylase release stimulated by cerulein or veratridine was reduced by 26.7 +/- 2 or 28.3 +/- 4%, respectively. CsA had no influence on the displacement of 125I-Bolton-Hunter-labeled CCK-8 from acinar CCK receptors. The ultrastructure of cellular organelles in isolated lobules was not altered after incubation with 0.1 mmol/l CsA for 60 min. Our data suggest that CsA interferes with protein-kinase-C-mediated signal transduction in isolated rat pancreatic acini, without affecting cAMP-dependent signalling.

Topics: Amylases; Animals; Calcimycin; Calcium; Culture Techniques; Cyclosporine; Male; Pancreas; Protein Kinase C; Rats; Rats, Wistar; Signal Transduction; Sincalide; Starvation

Modulation of feeding by opiates, putative satiety peptides, and dopamine was explored in the Chinese hamster, an animal that develops diabetes mellitus in certain inbred strains. Diabetic hamsters were hyperphagic relative to their nondiabetic controls, but both groups exhibited natural circadian variation in feeding. Starvation provoked hyperphagia of about 1-h duration in both groups. Naloxone and butorphanol had no effects on Chinese hamster feeding. Opiate receptor binding on Chinese hamster brains demonstrated no specific binding of naloxone or ethylketocyclazocine, but IR-dynorphin concentrations were comparable with that in rats. N-allylnormetazocine, a sigma-opiate receptor agonist, appeared to stimulate diabetic hamster feeding. Peptides reputed to have satiety effects in rats were without effect in Chinese hamsters: cholecystokinin, bombesin, somatostatin, and pancreatic polypeptide. Calcitonin limited feeding in both groups but may be nonspecific. Dopaminergic blockade by haloperidol also limited feeding, and diabetic hamsters were more sensitive to this. Although Chinese hamsters clearly can modulate their food intake when diabetic, we conclude that the opiatergic and peptidergic influences on feeding are very different from those in rats and may be of little importance.

Topics: Animals; Brain; Calcitonin; Circadian Rhythm; Cricetinae; Cyclazocine; Diabetes Mellitus; Dynorphins; Eating; Endorphins; Ethylketocyclazocine; Feeding Behavior; Haloperidol; Mesocricetus; Naloxone; Peptide Fragments; Phenazocine; Sincalide; Starvation