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Venom-isolated peptide action was compared with mammalian truncated glucagon-like peptide 1 (TGLP-1). The peptides studied included helospectin I, helodermin, exendin-3 and exendin-4. Helospectin 1 and helodermin are influenced by high-affinity secretin receptor reaction. Exendin-1, exendin-4 and TGLP are governed by exendin receptors in gastric cells due to variations in extent of peptide potency.

The canonical Wnt–β‐catenin pathway is important in normal development. Mutations in β‐catenin or proteins involved with regulating its phosphorylation or localization result in its nuclear accumulation where it activates its target genes and stimulates cell proliferation. This pathway is dysregulated in many different types of cancer, including gastric cancer (GC). Chibby (Cby) is a 14‐kDa protein that inhibits β‐catenin localization to the nucleus and represses β‐catenin‐induced transcriptional activity. In the current study, we examined the expression and function of Cby in normal and cancerous human gastric tissue. Reverse‐transcription polymerase chain reaction and immunohistochemistry revealed that Cby is expressed in human stomach and localized to glandular elements. Immunohistochemical staining intensity of Cby was decreased in GC tissue when compared with normal gastric epithelium. In AGS cells, a human gastric carcinoma cell line, Cby expression was low. Stable AGS cell transfectants overexpressing Cby were prepared. Cby overexpression did not affect proliferation rates or β‐catenin levels. However, confocal microscopy and subcellular fractionation studies revealed that Cby overexpression resulted in a small decrease in nuclear β‐catenin. Moreover, Cby overexpression caused a molecular weight shift in nuclear β‐catenin and resulted in decreased β‐catenin signaling in AGS cells as measured by the TopFlash assay. However, Cby overexpression did not affect c‐Myc protein levels. To conclude, Cby expression was decreased in GC samples and Cby expression altered β‐catenin localization in cultured GC cells. However, Cby did not affect cell proliferation rates or β‐catenin‐induced protein expression. Cby may be involved in the early events in the pathogenesis of GC. Chibby (Cby) is a 14‐kDa protein that inhibits β‐catenin localization to the nucleus and represses β‐catenin‐induced transcriptional activity. Cby expression was decreased in gastric cancer (GC) tissue and Cby expression altered β‐catenin localization in cultured GC cells. However, Cby did not affect cell proliferation rates or β‐catenin‐induced protein expression. [ABSTRACT FROM AUTHOR]

Examines the actions of low molecular weight guanine nucleotide-binding proteins' (Rab3) effector domain peptides on pepsinogen secretion. Interactions between Rab3 effector domain peptides and calcium, calcium adenosine 3',5'-cyclic monophosphate and guanine nucleotides; Signal transduction; Ras proteins.

Rab3D is a low molecular weight GTP-binding protein believed to be involved with regulated secretion in many cell types. In parotid, Rab3D is localized to secretory granule membranes or present in the cytosol as a complex with Rab escort protein. In the present study, we examined the redistribution of membrane-associated Rab3D during secretion in permeabilized parotid acini. When permeabilized acini were stimulated with calcium and cAMP, amylase release increased greater than twofold over basal. Quantitative immunoblotting of subcellular fractions revealed that Rab3D did not dissociate from parotid membranes during secretion. Immunohistochemical staining demonstrated that Rab3D co-localizes with amylase containing granules that are found in the apical pole of the cell. Upon stimulation with calcium and cAMP, Rab3D and amylase immunostaining of granules appeared to be more dispersed. However, Rab3D immunostaining was not observed on the plasma membrane and appeared to reside in the apical cytoplasm. To examine the role of Rab3D in amylase release, cytosolic extracts containing myc-tagged Rab3D and Rab3DQ81L, a GTP-binding mutant, were prepared and incubated with streptolysin O-permeabilized acini. Rab3D, but not Rab3DQ81L, bound to parotid membranes suggesting that Rab3D-binding to parotid membranes is guanine nucleotide-dependent. Moreover, wild-type and mutant Rab3D inhibited agonist-induced amylase release from permeabilized parotid acini. These observations indicate that in parotid acini, Rab3D does not dissociate from parotid membranes or redistribute to the plasma membrane during secretion, and may play an inhibitory role in regulated secretion. The fact that both wild-type Rab3D and the GTP-binding mutant inhibit amylase release suggests that binding of Rab3D to the membrane is not essential for secretory inhibition.