Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes

Abstract

The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive in vitro and in vivo studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.

Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis‐mediated pathways

“…PLTs contain copious amounts of mRNA, which may allow for PLT translational regulation and de novo synthesis of some proteins 42–44 . Comparison of the transcript profiles of RTPs and CSPs in plasma and PAS showed that the greatest differences between Day 5 RTP samples from baseline were found in transcripts directly associated with regulation of PLT apoptosis and CCKR pathways, which have been shown to influence the expression of downstream transcripts that affect cell survival, angiogenesis, and metabolic processes 45 . CCKRs, such as CCK1R and CCK2R, are coupled with G proteins 45 .…”

“…Comparison of the transcript profiles of RTPs and CSPs in plasma and PAS showed that the greatest differences between Day 5 RTP samples from baseline were found in transcripts directly associated with regulation of PLT apoptosis and CCKR pathways, which have been shown to influence the expression of downstream transcripts that affect cell survival, angiogenesis, and metabolic processes 45 . CCKRs, such as CCK1R and CCK2R, are coupled with G proteins 45 . The binding of CCK to CCK1R has been shown to induce mobilization of intracellular calcium and activation of protein kinase C via the phospholipase C, inositol triphosphate, and diacylglycerol pathways, respectively 45 .…”

“…CCKRs, such as CCK1R and CCK2R, are coupled with G proteins 45 . The binding of CCK to CCK1R has been shown to induce mobilization of intracellular calcium and activation of protein kinase C via the phospholipase C, inositol triphosphate, and diacylglycerol pathways, respectively 45 . Additionally, CCK1R activates the mitogen‐activated protein kinase (MAPK) and PI3K pathway.…”

“…Additionally, CCK1R activates the mitogen‐activated protein kinase (MAPK) and PI3K pathway. CCK1R also induces cyclic adenosine monophosphate (cAMP) accumulation, a well‐known process associated with PLT physiology 45 . The involvement of the CCKRs in PLT storage and dysfunction offer novel understandings to the potential mechanisms for loss of PLT function during storage and identify new potential mediators or targets for intervention.…”

The Carboxyl-Terminal Penta-Peptide Repeats of Major Royal Jelly Protein 3 Enhance Cell Proliferation

“…[21][22][23] The basic amino acid residues on the C-terminal side of the Q-N-x-N-[K/R] peptides may affect the activity of the penta-peptide in the same way as peptide hormones to lead to the higher cell proliferative activity of GST-TPR19. Peptide hormones, such as gastrin and cholecystokinin, induce cell proliferative activity through specific receptors 24,25) ; thus, identification of the cellular receptor for MRJP3 and the penta-peptide would be important to our understanding of the mechanisms underlying the proliferative activity. Alternatively, TPRs might internalized directly as a cell penetrating peptide, since they are rich in R and K residues so that they may behave similarly to Tat peptide of human immunodeficiency virus (HIV) and penetratin.…”