The phylogeny of the cholecystokinin/gastrin family

Johnsen, Anders H.; Rehfeld, J. F.

doi:10.1016/0167-0115(92)90560-h

Cited by 14 publications

(25 citation statements)

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“…The phylogenetic story shows that gastrointestinal hormones are very old, several hundred million years [23]. So far, the data also support the idea that each hormone family has evolved from a single ancestor.…”

Section: General Biological Features Of Gastrointestinal Hormonessupporting

confidence: 53%

Gastrointestinal hormone research – with a Scandinavian annotation

Rehfeld

2015

Scandinavian Journal of Gastroenterology

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Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization or differentiated posttranslational maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed outside the gut, some only in extraintestinal endocrine cells and cerebral or peripheral neurons but others also in other cell types. The extraintestinal cells may release different bioactive fragments of the same prohormone due to cell-specific processing pathways. Moreover, endocrine cells, neurons, cancer cells and, for instance, spermatozoa secrete gut peptides in different ways, so the same peptide may act as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions, but also constitute regulatory systems operating in the whole organism. This overview of gut hormone biology is supplemented with an annotation on some Scandinavian contributions to gastrointestinal hormone research.

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Section: General Biological Features Of Gastrointestinal Hormonessupporting

confidence: 53%

Gastrointestinal hormone research – with a Scandinavian annotation

Rehfeld

2015

Scandinavian Journal of Gastroenterology

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“…CCK is characterized by an evolutionary conserved biologically active C-terminal octapeptide (CCK-8) among vertebrates (198, 199), and Cck-ir cells have been observed in the intestine of most fish groups (174). Central or peripheral administration of sulfated CCK-8 suppresses food intake in goldfish (200) and channel catfish (14).…”

Section: Peripheral Signalsmentioning

confidence: 99%

Appetite-Controlling Endocrine Systems in Teleosts

et al. 2017

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Mammalian studies have shaped our understanding of the endocrine control of appetite and body weight in vertebrates and provided the basic vertebrate model that involves central (brain) and peripheral signaling pathways as well as environmental cues. The hypothalamus has a crucial function in the control of food intake, but other parts of the brain are also involved. The description of a range of key neuropeptides and hormones as well as more details of their specific roles in appetite control continues to be in progress. Endocrine signals are based on hormones that can be divided into two groups: those that induce (orexigenic), and those that inhibit (anorexigenic) appetite and food consumption. Peripheral signals originate in the gastrointestinal tract, liver, adipose tissue, and other tissues and reach the hypothalamus through both endocrine and neuroendocrine actions. While many mammalian-like endocrine appetite-controlling networks and mechanisms have been described for some key model teleosts, mainly zebrafish and goldfish, very little knowledge exists on these systems in fishes as a group. Fishes represent over 30,000 species, and there is a large variability in their ecological niches and habitats as well as life history adaptations, transitions between life stages and feeding behaviors. In the context of food intake and appetite control, common adaptations to extended periods of starvation or periods of abundant food availability are of particular interest. This review summarizes the recent findings on endocrine appetite-controlling systems in fish, highlights their impact on growth and survival, and discusses the perspectives in this research field to shed light on the intriguing adaptations that exist in fish and their underlying mechanisms.

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“…Therefore, in order to quantitate the expression we had to develop a new analysis that also would not be species-specific, as we wanted to examine the biosynthesis of nonsulfated CCK also in man and other mammals. That is pos sible because the CCK-8 sequence is identical in nearly all mammals [35]. As shown here, it is possible to meet this challenge by development of an immu noassay based on an antibody entirely specific for the N-terminal sequence of nonsulfated CCK-8.…”

Section: Discussionmentioning

confidence: 97%

Measurement of nonsulfated cholecystokinins

Agersnap

Rehfeld

2014

Scandinavian Journal of Clinical and Laboratory Investigation

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Most proteins undergo posttranslational modifications that govern the function of the protein. In synchrony, correspondingly unmodified proteins that are functionally silent or act differently may also be synthesized. The gut hormone precursor, procholecystokinin (proCCK) is an example of a protein that is heavily modified. An essential modification is O-sulfation of Y₇₇, which is necessary for the gallbladder emptying effect of CCK peptides via the CCKA-receptor. In order to examine possible in vivo synthesis also of nonsulfated CCK, we have established a two-step analysis that requires tryptic cleavage at a defined processing site in proCCK (R₇₅-D₇₆) followed by monospecific RIA-measurement of the then exposed nonsulfated N-terminal sequence of CCK-8 (DYMGW…). The analysis shows that endocrine cells in the gut synthesize nonsulfated CCK peptides (-58, -33, -22, and -8) in the order of 20-35% of the corresponding sulfated CCKs. Since nonsulfated CCK peptides are full agonists of the CCKB-receptor, the assay has revealed a hitherto unrecognized gut hormonal peptide system. The assay may prove useful in the diagnosis and control of diseases with hyperCCKemia. This includes CCK-producing neuroendocrine tumors such as the recently described CCKomas and medullary thyroid C-cell carcinomas.

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The phylogeny of the cholecystokinin/gastrin family

Cited by 14 publications

References 0 publications

Gastrointestinal hormone research – with a Scandinavian annotation

Gastrointestinal hormone research – with a Scandinavian annotation

Appetite-Controlling Endocrine Systems in Teleosts

Measurement of nonsulfated cholecystokinins

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