The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

Beinfeld, Margery C.; Meyer, Dieter; Eskay, Robert L.; Jensen, Robert T.; Brownstein, Michael J.

doi:10.1016/0006-8993(81)90031-7

Cited by 523 publications

(134 citation statements)

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“…These results, taken together with the observation that both CCK 22 and CCK 8 are secreted by wild type STC-1 and Rin5F, 4 suggest that CCK 8 and CCK 22 are both end products of pro-CCK processing which do not readily interconvert and that they are produced by independent processing pathways of pro-CCK. These results are consistent with the hypothesis that the differences in processing of pro-CCK observed in brain and gut are related to tissue differences in expression or activity of PC1 and PC2.…”

Section: Discussionmentioning

confidence: 76%

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Yoon

Beinfeld

1997

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 76%

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Yoon

Beinfeld

1997

Journal of Biological Chemistry

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“…Mature pigs weighing [10][11][12][13][14][15][16][17][18][19][20] kg were purchased from Bio-Medical Associates (Friedensburg, PA). They were sacrificed by injecting an overdose of pentobarbital into the heart.…”

Section: Methodsmentioning

confidence: 99%

“…Among these, cholecystokinin (CCK) appears to be unique in that comparably high concentrations are found in neuronal and in mucosal tissues (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The various CCK-related peptides, immunochemically distinguishable by a variety of antisera (6,7,16), have not been shown to be extracted from tissues with equal efficiency by any single extractant.…”

mentioning

confidence: 99%

Post-translational processing of cholecystokinin in pig brain and gut.

Eng¹,

Shiina²,

Straus³

et al. 1982

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

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A sequential extraction method employing methanol extraction of the COOH-terminal fragments of cholecystokinin (CCK) from pig tissues followed by HCl extraction of intact CCK and its NH2-terminal fragments is described. Radioimmunoassay of extracts and their fractionation by Sephadex chromatography and HPLC demonstrate that the distributions ofCOOHterminal and NH2-terminal immunoreactivities among various regions ofbrain are similar and independent ofthe concentrations in individual regions. The distribution in gut differs from that in brain. Greatest concentrations of CCK immunoreactivity are located in cortical tissue in the brain and in duodenal mucosa in gut. Both brain and gut contain CCK octapeptide (CCK8) and an NH2-terminal fragment that is likely to be desoctapeptide-CCK33. Intact CCK33 is extractable from gut but not from brain. Brain contains another NH2-terminal immunoreactive molecule lacking COOH-terminal immunoreactivity that may be a peptide with a COOH-terminal extension, as has been described for gastrin, or one that may not be derived from a CCK33-like precursor. This peptide is much less prominent in gut, or may be nonexistent there. The failure to find CCK33 in the brain and the presence in the brain of this as-yet-uncharacterized NH2-terminal peptide raises the question as to whether the differences between neuronal and mucosal tissues are a consequence ofdifferences in post-translational processing or in the DNA templates.It is now generally accepted that there are several peptides common to the brain and to the gastroenteropancreatic axis. Among these, cholecystokinin (CCK) appears to be unique in that comparably high concentrations are found in neuronal and in mucosal tissues (1-18). The various CCK-related peptides, immunochemically distinguishable by a variety of antisera (6, 7, 16), have not been shown to be extracted from tissues with equal efficiency by any single extractant. In this study we describe optimal methods for sequential extraction and radioimmunoassay (RIA) of the CCK peptides by using antisera specific for the NH2 terminus and COOH terminus, further characterize the properties of these peptides in different physicochemical systems, and determine whether, assuming a common precursor for all CCK forms, there are differences in the post-translational processing in the different tissues. MATERIALS AND METHODSMature pigs weighing 10-20 kg were purchased from Bio-Medical Associates (Friedensburg, PA). They were sacrificed by injecting an overdose of pentobarbital into the heart. The brain and sections ofsmall intestine were quickly removed, dissected, and placed on dry ice. The frozen tissues were stored at -70°C until extraction. In some studies equivalent portions of brain and gut tissues were maintained at ambient temperature for 60 min before freezing.Tissues were weighed and extracted with 10 vol of absolute methanol in autoclaved Teflon grinders. The extract suspensions were filtered by suction through Whatman no. 50 filter paper. The filter cakes together with...

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“…The question was approached by examining the action of 5-HT on the release of cholecystokinin-like immunoreactivity (CCK-LI) from cerebral tissue. It is known that CCK is widely distributed throughout the brain (Beinfeld et al, 1981;Emson & Marley, 1983), the highest amounts being found in the cerebral cortex and in limbic areas possibly involved in the expression of anxiety.…”

Section: Introductionmentioning

confidence: 99%

Cholecystokinin release mediated by 5‐HT₃ receptors in rat cerebral cortex and nucleus accumbens

Paudice

Raiteri

1991

British J Pharmacology

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1 The effects of 5-hydroxytryptamine (5-HT) on the release of cholecystokinin-like immunoreactivity (CCK-LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mM KCl. 2 In both areas 5-HT, tested between 0.1 and 100 nm, increased the calcium-dependent, depolarizationevoked CCK-LI release in a concentration-related manner. The concentration-response curves did not differ significantly between the two brain areas (EC50: 0.4 + 0.045 nm and 0.48 + 0.053 nm, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nm 5-HT).3 The 5-HT,/5-HT2 receptor antagonist methiothepin (300 nM) did not affect the CCK-LI release elicited by 10nm 5-HT. However, the effects of 10nm 5-HT were antagonized in a concentration-dependent manner by the 5-HT3 receptor antagonists (3a-tropanyl)-lH-indole-3-carboxylic acid ester 0.1-100 nM; IC50: 3.56 + 0.42 nm in the cortex and 3.90 + 0.50 nm in the n. accumbens) and ondasetron (IC50: 8.15 + 0.73nm in the cerebral cortex). 5-HT (10nM) was also strongly antagonized by l00nM laH, 3a5aH-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222) another blocker of the 5-HT3 receptor. Moreover, the 5-HT3 receptor agonist 1-phenylbiguanide (tested in the cerebral cortex between 0.1 and 100nM) enhanced CCK-LI release in a manner almost identical to that of 5-HT (EC5o = 0.64 + 0.071 nM).4 It is concluded that 5-HT can act as a potent releaser of CCK-LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5-HT3 type situated on the CCK-releasing terminals. This interaction may provide a rationale for the clinical development of both 5-HT3 and CCK receptor antagonists as novel anxiolytic drugs.

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The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

Cited by 523 publications

References 11 publications

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Post-translational processing of cholecystokinin in pig brain and gut.

Cholecystokinin release mediated by 5‐HT₃ receptors in rat cerebral cortex and nucleus accumbens

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The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay

Cited by 523 publications

References 11 publications

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Prohormone Convertase 1 Is Necessary for the Formation of Cholecystokinin 8 in Rin5F and STC-1 Cells

Post-translational processing of cholecystokinin in pig brain and gut.

Cholecystokinin release mediated by 5‐HT3 receptors in rat cerebral cortex and nucleus accumbens

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Cholecystokinin release mediated by 5‐HT₃ receptors in rat cerebral cortex and nucleus accumbens