Interaction of caerulein and secretin on pancreatic size and composition in rat.

Solomon, Travis E.; Petersen, H; Elashoff, Janet D.; Grossman, M. I.

doi:10.1152/ajpendo.1978.235.6.e714

Cited by 107 publications

(59 citation statements)

References 16 publications

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“…Various agents such as CCK, bombesin, and epidermal growth factor influence growth in the adult pancreas (28)(29)(30)(31)(32)(33)(34)(35). Undoubtedly, these agents act upon the immature pancreas as well, regulating DNA, RNA, and protein synthesis, and therefore growth in a coordinated manner.…”

Section: Discussionmentioning

confidence: 99%

DNA and Protein Synthesis in Developing Rat Pancreas

et al. 1987

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ABSTRACT. To define developmental patterns, we determined the rate of protein and DNA synthesis in rat pancreas at birth, 1, 2, 3, 7, 10, 14, 21, 28 days, 2 months, 3 months, and in adults. Fragments of freshly minced pancreas were incubated with [3H]-thymidine and [14Cj-leucine and the DNA and protein synthesis rates were measured. We found that 1) DNA content was lowest at birth, rose through day 3, plateaued at about 8 mg/g wet weight through day 14, then slowly decreased to the adult value of about 5 mg/g at 2 months; 2) protein content, although high at birth, decreased rapidly to a value of 80 mg/g at day 3 and slowly rose to the adult value of 160 mglg; 3) protein synthesis, low at birth, rapidly increased to about five times the adult value by day 3, and remained elevated for the 1st month; 4) DNA synthesis was 15 times the adult rate at birth, increased to 30 times at 3 days of age, then declined slowly in an exponential fashion to the adult value. We conclude that the pancreas at birth is poised biosynthetically to undergo a rapid hyperplastic and hypertrophic response, and this process reaches a maximal rate at about 3 days of age. (Pediatr Res 22: 34-38,1987) Abbreviations MEM, minimum essential medium BSA, bovine serum albumin SA, specific activity PCA, perchloric acid CCK, cholecystokinin Numerous studies have defined the structural and functional development of rodent exocrine pancreas. Similarly, a number of studies has evaluated the effects of various agents thought to be trophic for the exocrine pancreas on DNA and protein content of the developing pancreas. Previous studies, however, have evaluated total DNA and protein content, but not actual rates of synthesis of DNA and protein at various ages (1-5). Since cellular content of biomolecules reflects the opposing actions of synthesis and degradation, the true effects of any agent tested may be masked when total organ content is measured. In addition, increases in DNA synthesis in the stomach and small intestine can be observed before an increase in DNA content itself (6). A further difficulty is that technically it is extremely difficult to remove the entire pancreas from neonatal rats. Accordingly, we have evaluated DNA and protein synthesis in rat pancreas of various ages and compared synthetic rates to those found in the adult animal. Not surprisingly, the synthesis rates of both were found to be considerably higher in the immature animal than in the mature animal. MATERIALS AND METHODSSprague Dawley rats obtained from King Laboratories, Madison, WI were used for all studies and were kept under controlled light and temperature conditions. After birth, the rats were not disturbed except for the addition of food and water. Pups were sacrificed at the stated ages a 2 h for ages up to 72 h, and a 1 day for ages 1 to 4 wk. Adult animals (males only) were 4-6 months old. The date of birth was designated as day 0. Before weaning, rats were not fasted; after weaning (day 21), rats were fasted overnight before sacrifice, but allowed free access t...

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Section: Discussionmentioning

confidence: 99%

DNA and Protein Synthesis in Developing Rat Pancreas

et al. 1987

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“…Some of these drugs had a tendency to induce abdominal cramping, nausea and diarrhea, all explained by physiologic effects of this hormone. In addition, there has been a concern about potential induction of pancreatitis, with CCK (caerulein) hyperstimulation being a prominent investigative strategy to induce experimental pancreatitis in rodents, 21 and the trophic effect of this hormone to stimulate pancreatic cell growth, 22,23 with concern about induction and/or progression of pancreatic cancer. These toxic effects have not been observed in clinical trials with these drugs.…”

Section: Cholecystokinin Physiologymentioning

confidence: 99%

Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

et al. 2016

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The gastrointestinal (GI) tract has a central role in nutritional homeostasis, as location for food ingestion, digestion and absorption, with the gut endocrine system responding to and regulating these events, as well as influencing appetite. One key GI hormone with the full spectrum of these activities is cholecystokinin (CCK), a peptide released from neuroendocrine I cells scattered through the proximal intestine in response to fat and protein, with effects to stimulate gall bladder contraction and pancreatic exocrine secretion, to regulate gastric emptying and intestinal transit, and to induce satiety. There has been interest in targeting the type 1 CCK receptor (CCK1R) for drug development to provide non-caloric satiation as an aid to dieting and weight loss; however, there have been concerns about CCK1R agonists related to side effects and potential trophic impact on the pancreas. A positive allosteric modulator (PAM) of CCK action at this receptor without intrinsic agonist activity could provide a safer and more effective approach to long-term administration. In addition, CCK1R stimulus-activity coupling has been shown to be negatively affected by excess membrane cholesterol, a condition described in the metabolic syndrome, thereby potentially interfering with an important servomechanism regulating appetite. A PAM targeting this receptor could also potentially correct the negative impact of cholesterol on CCK1R function. We will review the molecular basis for binding natural peptide agonist, binding and action of small molecules within the allosteric pocket, and the impact of cholesterol. Novel strategies for taking advantage of this receptor for the prevention and management of obesity will be reviewed.International Journal of Obesity Supplements (2016) 6, S22-S27; doi:10.1038/ijosup.2016.5 INTRODUCTIONThe prevalence of obesity has been progressively increasing throughout the United States and around the world, contributing to a parallel increase in the prevalence of type 2 diabetes mellitus and its associated comorbidities. 1 These problems have been responsible for extraordinary morbidity, suffering, loss in productivity and premature mortality. In spite of major efforts to develop effective weight reduction diets, diet aids, medications, medical devices and surgical procedures, the trajectory for this continues in the wrong direction. Bariatric surgery has proven to be quite effective in patients with morbid obesity; 2 however, this is quite expensive and not scalable, certainly not keeping up with the increasing prevalence of the most severe end of this clinical continuum. The activity of acute dieting and exercise has been similarly effective in inducing weight loss; however, it has not been durable, with an extremely high incidence of regaining weight to or even beyond the starting point. After a long hiatus in approved drugs, three new diet medications have recently been approved, 3-5 but all carry concerns about safety, and there are requirements for registration and careful clinical follow-up, re...

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“…Secretin stimulates the secretion of bicarbonate, water, and electrolytes from the pancreatic ductal epithelium in response to gastric acid and fatty acids in the duodenum (Meyer et al 1970, Watanabe et al 1986). In rat, secretin has been demonstrated to potentiate the effect of cholecystokinin in the stimulation of enzyme secretion from the pancreatic acinar cells (Rausch et al 1985) and promotes pancreatic growth (Solomon et al 1978(Solomon et al , 1983(Solomon et al , 1987.…”

Section: Secretin Serves As a Gastrointestinal Hormone In Both Nonmammentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Secretin/secretin receptors

Tam

Lee

Jin

et al. 2014

Journal of Molecular Endocrinology

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In mammals, secretin is a 27-amino acid peptide that was first studied in 1902 by Bayliss and Starling from the extracts of the jejunal mucosa for its ability to stimulate pancreatic secretion. To date, secretin has only been identified in tetrapods, with the earliest diverged secretin found in frogs. Despite being the first hormone discovered, secretin's evolutionary origin remains enigmatic, it shows moderate sequence identity in nonmammalian tetrapods but is highly conserved in mammals. Current hypotheses suggest that although secretin has already emerged before the divergence of osteichthyans, it was lost in fish and retained only in land vertebrates. Nevertheless, the cognate receptor of secretin has been identified in both actinopterygian fish (zebrafish) and sarcopterygian fish (lungfish). However, the zebrafish secretin receptor was shown to be nonbioactive. Based on the present information that the earliest diverged bioactive secretin receptor was found in lungfish, and its ability to interact with both vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide potently suggested that secretin receptor was descended from a VPAC-like receptor gene before the Actinopterygii-Sarcopterygii split in the vertebrate lineage. Hence, secretin and secretin receptor have gone through independent evolutionary trajectories despite their concurrent emergence post-2R. A functional secretin-secretin receptor axis has probably emerged in the amphibians. Although the pleiotropic actions of secretin are well documented in the literature, only limited information of its physiological functions in nonmammalian tetrapods have been reported. To decipher the structural and functional divergence of secretin and secretin receptor, functional characterization of the ligandreceptor pair in nonmammals would be the next perspective for investigation.

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Interaction of caerulein and secretin on pancreatic size and composition in rat.

Cited by 107 publications

References 16 publications

DNA and Protein Synthesis in Developing Rat Pancreas

DNA and Protein Synthesis in Developing Rat Pancreas

Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

MOLECULAR EVOLUTION OF GPCRS: Secretin/secretin receptors

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