Cholecystokinin elicits Satiety in Rats with Open Gastric Fistulas

Gibbs, James; Young, Robert C.; Smith, Gerard P.

doi:10.1038/245323a0

Cited by 510 publications

(163 citation statements)

References 8 publications

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“…The observation of Gibbs et al (11,12) that injection of purified CCK or CCK-8 evoked satiety, although pentagastrin and secretin did not, has suggested a negative feedback mechanism from the gastrointestinal tract as the causative mechanism. The concept that the'CCK peptides that appear to be endogenous in the brain may be neuroregulators is an intriguing one.…”

Section: Discussionmentioning

confidence: 99%

Cholecystokinin and its COOH-terminal octapeptide in the pig brain.

Müller¹,

Straus²,

Yalow³

1977

Proc. Natl. Acad. Sci. U.S.A.

174

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Purification was done by using starch gel electrophoresis for labeled gastrin (4) and by using adsorption to and elution from Quso G32 for labeled CCK (4). Radioimmunoassay. Radioimmunoassay was done with a 2.5-ml incubation volume. The standard diluent was generally 0.02 M barbital, pH 8.6, containing either 0.2 g of bovine serum albumin per 100 ml or 2% fetal bovine serum. The concentration of the labeled gastrin tracer and the labeled CCK tracer was generally <0.5 pg/ml and <10 pg/ml, respectively. The crossreactivities of PGI, intact CCK, and CCK-8 were studied with each of the antisera. Radioimmunoassay of extracts, starch-block eluates, and Sephadex fractions was performed by using methods quite similar to those established in our laboratory for other hormones (4, 5).Brain Extracts. Immediately after death, specimens for extraction were taken from various portions of the brain of the pig including the cortex, the cerebellum, and the pons. The tissues were sectioned while still frozen, 0.1 M HCI or distilled water was added to produce a concentration of 0.1 g wet weight of tissue per ml, the solutions were boiled for 3 min, and then the tissues were homogenized in their extraction solution by using a Teflon tissue grinder. The extracts were assayed directly with each antiserum and were also fractionated by starch block electrophoresis and on Sephadex columns using radioactive marker molecules to locate the positions of the void volume and the salt peak. These methods were similar to those described from our laboratory for the gastrin peptides (6, 7). RESULTSThe crossreactivities of PGI, CCK, CCK-8, and water and acid extracts of the pig cerebral cortex were studied with each of the antisera (Fig. 1). The brain extracts crossreacted strongly with the goat antiserum against porcine CCK which had good sensitivity for the detection of porcine CCK but low sensitivity for the detection of PGI and CCK-8; this extract also crossreacted strongly with the rabbit antiserum against G-(14-17)-which had good sensitivity for the detection of PGI and CCK-8 but much poorer sensitivity for the detection of intact CCK. These findings suggest that the brain extract contains both CCK-like and CCK-8-like peptides. No detectable immunoreactivity was observed for the pons or cerebellum extracts with either antiserum. The 0.1 M HC1 extract of the cortex appeared to contain 0.4 ,ug of CCK per g wet weight of tissue by using the goat anti-CCK serum and 0.03 ,ug of CCK-8 per g wet weight of tissue by using rabbit B antiserum. The boiling water extraction resulted in apparent concentrations of 0.2 ,ug of CCK per g wet weight of tissue and 0.2 ,ug of CCK-8 per g wet weight of tissue. Thus, 0.1 M HCl is more efficient for the extraction of the CCK-like peptide, but water is more efficient for the extraction of the CCK-8 like peptide from the brain.

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Section: Discussionmentioning

confidence: 99%

Cholecystokinin and its COOH-terminal octapeptide in the pig brain.

Müller¹,

Straus²,

Yalow³

1977

Proc. Natl. Acad. Sci. U.S.A.

174

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“…These include cholecystokinin (CCK), glucagon-like peptide 1 (GLP1), apolipoprotein A-IV, enterostatin, gastrin-releasing peptide (a member of the bombesin family), oxyntomodulin, amylin and peptide YY. CCK administration causes reduced food intake, 55 while antagonists to CCK A receptors substantially increase food intake; 56 thus, endogenous CCK has a role in controlling meal size. The satiety-inducing effects of CCK require an intact vagus nerve.…”

Section: Vagal Mucosal Afferentsmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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“…1A) with some fibers oriented toward the ventral portion of the brain stem. These cells had variable shapes but usually were round or spindle-shaped with an average length of [15][16][17][18][19][20] ,m (Fig. 1C).…”

mentioning

confidence: 99%

Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

Innis¹,

Corrêa²,

Uhl³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

298

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Cholecystokinin octapeptide-like (CCK-OPlike) immunoreactivity was localized in the rat brain by using the indirect immunofluorescence method. Specificity in immunohistochemical studies was demonstrated by the virtual elimination of staining with either preimmune sera or sera preadsorbed with CCK-OP and by the achievement of similar fluorescent patterns with two different primary anti-CCK-OP sera. CCK-OP-like fluorescence was localized in neuronal cell bodies, fibers, and varicose terminals. The most dense collections of CCK-OP cells occurred in the periaqueductal gray and in the dorsomedial hypothalamus. Substantial numbers of cells and fibers also were present in the medial/dorsal and perirhinal cortex; more limited groups of cells were found in the pyramidal layer of the hippocampus and in the dorsal raphe.Immunoreactivity related to cholecystokinin (CCK), a 33-amino acid polypeptide originally isolated from the duodenum (1), has been found in the brains of several vertebrate species including man (2, 3) and shown to be attributable largely to the COOH-terminal octapeptide (CCK-OP), although native cholecystokinin is also present in the brain (3, 4). In rat brain, 75% of immunoreactive CCK represents CCK-OP (unpublished data). In preliminary histochemical studies, CCK immunoreactivity has been observed in rabbit cerebral cortex (5). We now report detailed immunohistochemical localizations of CCK-OP immunoreactivity in the rat brain.MATERIALS AND METHODS Immunofluorescence. CCK-OP was visualized by the indirect immunohistofluorescence method of Coons (6) as described (7). Sprague-Dawley male rats (100 g) were injected intracerebroventricularly with 50 jig of colchicine (Sigma) dissolved in 20 jil of 0.9% NaCl 48 hr before sacrifice. Animals were perfused through the heart for 10 sec with ice cold isotonic saline and then for 5-10 min with ice cold phosphate-buffered 4% depolymerized paraformaldehyde solution prepared according to Pease (8). Brains were postfixed for 90 min in this perfusate and then soaked for at least 24 hr in 7% sucrose/0.6 M phosphate buffer, pH 7.4. Brain slabs approximately 0.5 mm thick were rapidly frozen onto cryostat chucks by using liquid nitrogen. Sections (16 jim) were cut at -20°C in a Harris cryostat and thaw-mounted onto gelatin/chrome alum-coated slides. Sections were stained at 37°C for 30 min with primary antisera diluted 1:25 with phosphate-buffered saline (Pi/NaCI) containing 0.2% Triton X-100. After three 5-min washes with Pi/NaCI/0.5% Triton, the sections were exposed for 15 min at 37°C to fluorescein-conjugated guinea pig antibody against rabbit IgG (Cappel Laboratories) diluted 1:40 with Pi/NaCl/ 0.1% Triton. The sections were then washed three times (5 min each) in P1/NaCl/0.2% Triton, dipped in H20, and mounted with 0.5 M sodium bicarbonate buffer (pH 8.4) diluted 1:1 with glycerol.

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Cholecystokinin elicits Satiety in Rats with Open Gastric Fistulas

Cited by 510 publications

References 8 publications

Cholecystokinin and its COOH-terminal octapeptide in the pig brain.

Cholecystokinin and its COOH-terminal octapeptide in the pig brain.

Extrinsic primary afferent signalling in the gut

Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain.

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