Exocytosis in various secretory cells is regulated by Ca2+ signaling. In this minireview, I will introduce our recent approach, which we have termed comparative biology of exocytosis, to the study of Ca2+-dependent secretion in such cells. In this approach, we quantify and compare the secretory process in different cell types (neurons, endocrine cells, and exocrine cells, with the same techniques. This approach benefits from the fact that the biochemistry and ultrastructure of these cells are relatively well characterized and it is expected to be particularly revealing because of the marked differences in the properties of exocytosis thought to exist among different secretory cells. The first part of this article deals with the mechanism by which Ca2+ signaling regulates exocytosis in exocrine cells, and the second part deals more generally with the diversity in the kinetics of the exocytotic machinery among different types of cells and secretory vesicles.
Biochemistry ; Biology ; Endocrine Cells ; Exocytosis* ; Kinetics ; Secretory Pathway ; Secretory Vesicles

The internal morphology of the right and left atria of rabbit, cat, pig, and human, particularly on the luminal structures of the auricle, were observed by stereomicroscope improving corrosion casting method using latex. Structures of the right auricular casts markedly differ from those of the left side, consisting of defined surface sturctures with distinct folds and branching patterns. The main atrial region consists of smooth surfaced single mass of the latex, and the auricular region is characterized by well developed branching patte and delicate small folds. The results of this study indicate that auricula have well organized duct-like luminal structures and many small pouches (out-pocketings) expanding the internal wall of the duct-like structures and small pouches. The endocardial nuclear imprints on the surface of the folds in the auricular region appeared larger and deeper than those on the atrium proper region of the atrial cast. These morphological observation will be aid in understanding structures of auricular lumen, regional differences of the endocardium and their function to the secretory process of atrial natriuretic peptide (ANP) release.
Animals* ; Cats ; Corrosion Casting* ; Corrosion* ; Endocardium ; Humans ; Latex ; Methods* ; Phenobarbital* ; Secretory Pathway

Protein transport from endoplasmic reticulum (ER) to Golgi apparatus has long been known to be a central process for protein quality control and sorting. Recent studies have revealed that a large number of signal molecules are involved in regulation of membrane trafficking through ER, ER-Golgi intermediate compartment and Golgi apparatus. These molecules can significantly change the transport rate of proteins by regulating vesicle budding and fusion. Protein transport from ER to Golgi apparatus is not only controlled by signal pathways triggered from outside the cell, it is also regulated by feedback signals from the transport pathway.
Endoplasmic Reticulum ; metabolism ; Golgi Apparatus ; metabolism ; Humans ; Protein Transport ; physiology ; Secretory Pathway ; Signal Transduction

There are numerous studies on transepithelial transports in duct cells including Cl and/or HCO3. However, studies on transepithelial K transport of normal duct cells in exocrine glands are scarce. In the present study, we examined the characteristics of K currents in single duct cells isolated from guinea pig pancreas, using a whole-cell patch clamp technique. Both Cl and K conductance were found with KCl rich pipette solutions. When the bath solution was changed to low Cl, reversal potentials shifted to the negative side, 75 4 mV, suggesting that this current is dominantly selective to K. We then characterized this outward rectifying K current and examined its Ca2 dependency. The K currents were activated by intracellular Ca2. 100 nM or 500 nM Ca2 in pipette significantly (P< 0.05) increased outward currents (currents were normalized, 76.8 7.9 pA, n=4 or 107.9 35.5 pA, n=6) at 100 mV membrane potential, compared to those with 0 nM Ca2 in pipette (27.8 3.7 pA, n=6). We next examined whether this K current, recorded with 100 nM Ca2 in pipette, was inhibited by various inhibitors, including Ba2, TEA and iberiotoxin. The currents were inhibited by 40.4 % (n=3), 87.0 % (n=5) and 82.5 % (n=9) by 1 mM Ba2, 5 mM TEA and 100 nM iberiotoxin, respectively. Particularly, an almost complete inhibition of the current by 100 nM iberiotoxin further confirmed that this current was activated by intracellular Ca2. The K current may play a role in secretory process, since recycling of K is critical for the initiation and sustaining of Cl or HCO3 secretion in these cells.
Animals ; Baths ; Exocrine Glands ; Guinea Pigs ; Membrane Potentials ; Pancreas ; Pancreatic Ducts* ; Recycling ; Secretory Pathway ; Tea

PURPOSE: Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility. MATERIALS AND METHODS: In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls. RESULTS: Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3′-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (p(corr)=0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (p(corr)=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05). CONCLUSION: Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.
Brain ; Chromogranin B ; Female ; Haplotypes ; Humans ; Male ; Mental Disorders ; Neuropeptides ; Odds Ratio ; Peptide Hormones ; Polymorphism, Single Nucleotide ; Schizophrenia* ; Secretory Pathway

While fluoxetine (FXT) is a frequently prescribed selective serotonin reuptake inhibitor (SSRI), with few major side-effects; altered serotonergic transmissions in hypothalamic pathways might lead to a distressing, and often embarrassing, manifestation of galactorrhea by altering prolactin release in those on FXT. We report here a case of FXT-induced hyperprolactinemic galactorrhea developing late into treatment on a stable regimen, who responded well to subsequent replacement with sertraline. Based on present finding, we suggest that while SSRIs may share similar mechanisms of action, there exist individual differences in their effects on prolactin secretion pathways.
Female ; Fluoxetine* ; Galactorrhea* ; Hyperprolactinemia ; Individuality ; Obsessive-Compulsive Disorder* ; Pregnancy ; Prolactin ; Secretory Pathway ; Serotonin ; Serotonin Uptake Inhibitors ; Sertraline

Cortex mori (Morus alba L. : Sangbaikpi), the root barks of mulberry tree, has been used as an antiphlogistic, diuretic, and expectorant in herbs. Previous studies have demonstrated that the phenolic extracts of Cortex mori have hypotensive, hypoglycemic, antifungal, antiviral, antiinflammatory, and anticancer effects, and the hot water extract from Cortex mori has the inhibitory effects on compound 48/80-induced mast cell degranulation and histamine release from rat mast cells (RMCs). Colchicine, an alkaloid found in the crocuslike plant, has been known as an inhibitor of mitosis and microtubule assembly by formation of tubulin-colchicine complex. The purpose of this study was to examine the effect of Cortex mori on the colchicine-induced mast cell degranulation, histamine release, and calcium uptake as a part of the study of the role of microtubules in the mast cell secretory process and the inhibitory mechanism of Cortex mori. The results were summarized as follows. Cortex mori sigificantly inhibited the colchicine-induced cytomorphologi-cal changes of RMCs such as displacement of the nucleus to the periphery, pronounced anisodiametry of the cytoplasm, stubby or broad cytoplasmic mass. Colchicine induced histamine release from RMCs and calcium uptake into RMCs, but it was not significantly , compared to those of negative control group. Cortex mori inhibited the colchicine-induced histamine release from RMCs and calcium uptake into RMCs. Above results, it is suggested that Cortex mori has an activity to inhibit the colchicine-induced cytomorphological changes by inhibition of calcium uptake into the mast cells.
Animals ; Calcium ; Colchicine ; Cytoplasm ; Histamine ; Histamine Release ; Mast Cells* ; Microtubules ; Mitosis ; Morus ; Phenol ; Plants ; Rats ; Secretory Pathway ; Trees ; Water

Calcium has versatile roles in diverse physiological functions. Among these functions, intracellular Ca²⁺ plays a key role during the secretion of salivary glands. In this review, we introduce the diverse cellular components involved in the saliva secretion and related dynamic intracellular Ca²⁺ signals. Calcium acts as a critical second messenger for channel activation, protein translocation, and volume regulation, which are essential events for achieving the salivary secretion. In the secretory process, Ca²⁺ activates K⁺ and Cl⁻ channels to transport water and electrolyte constituting whole saliva. We also focus on the Ca²⁺ signals from intracellular stores with discussion about detailed molecular mechanism underlying the generation of characteristic Ca²⁺ patterns. In particular, inositol triphosphate signal is a main trigger for inducing Ca²⁺ signals required for the salivary gland functions. The biphasic response of inositol triphosphate receptor and Ca²⁺ pumps generate a self-limiting pattern of Ca²⁺ efflux, resulting in Ca²⁺ oscillations. The regenerative Ca²⁺ oscillations have been detected in salivary gland cells, but the exact mechanism and function of the signals need to be elucidated. In future, we expect that further investigations will be performed toward better understanding of the spatiotemporal role of Ca²⁺ signals in regulating salivary secretion.
Calcium Signaling ; Calcium ; Chloride Channels ; Inositol ; Inositol 1,4,5-Trisphosphate Receptors ; Protein Transport ; Saliva ; Salivary Glands ; Salivation ; Second Messenger Systems ; Secretory Pathway ; Water

BACKGROUND: Ground glass hepatocytes are unique histological feature of chronic hepatitis B viral infection. The pre-S1 region of large surface protein has been shown to regulate assembly, processing, and secretion of HBsAg. The purpose of this study was to elucidate that a mutant form of pre-S1 affects this normal secretory pathway and is responsible for ground glass hepatocyte. METHODS: We examined HBV sequences spanning the pre-S region from a patients with HBeAg positive chronic HBV infection. HBV DNA was extracted from serum, cloned, and sequenced and determined the intrahepatic viral composition by extracting HBV DNA from paraffin embedded liver tissue. To analyze the viral population of single groundglass hepatocytes, we used the technique of laser capture microdissection to isolate individual hepatocytes from biopsy specimen. Groundglass hepatocytes that stained positively with anti-HBs and normal hepatocytes were harvested individually and their subjected HBV DNA sequences were analyzed. To define the responsible mutations for the HBsAg secretion, we introduced the mutant gene into molecular clone of wildtype (adwR9) and assayed their HBsAg amounts in the transfected cell supernatants by ELISA. RESULTS: Of 12 clones in serum analyzed, 9 clones had identical wild type sequences in the N-terminal region of the pre-S1 protein which plays an important role in the secretion and retention of HBV envelope proteins. One of the wild type clones has deletion within pre-S2 region. 3 identical mutant clones were isolated. Mutant type clones were predominant groundglass hepatocytes. CONCLUSIONS: We speculate that a mutant form of the HBV pre-S1 protein may result in the formation of ground-glass hepatocytes. Expression of abnormal pre-S1 may lead to its retention and accumulation within hepatocytes.
Base Sequence ; Biopsy ; Clone Cells ; DNA ; Enzyme-Linked Immunosorbent Assay ; Glass ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic ; Hepatocytes* ; Humans ; Laser Capture Microdissection ; Liver ; Paraffin ; Secretory Pathway

BACKGROUND: CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroendocrine tumors and its immunoreactivity has also been reported in gastrointestinal neuroendocrine tumors. However, the normal distribution of CD99 reactive cells in gastrointestinal mucosa and their function are not fully understood. METHODS: We performed an immunohistochemical study using antibodies to CD99 and gastrin on formalin fixed and paraffin embedded tissue of the stomach. RESULTS: CD99 were strongly expressed in the gastric glands of neonate (3/3) and infant (1/1) cases but not detected in the fetal period (0/30). In adults, CD99 was observed in 36.8% (7/19). The number of CD99 positive cells were fewer in adult (3.48+/-6.43) than in neonate (5.66+/-0.58) and infant (11.33+/-2.21). CD99 was mostly located along the cytoplasmic membrane of glandular cells but cytoplasmic expression was also evident in neonate and infant cases. The G cells and CD99 expressed cells were reduced in the area showing intestinal metaplasia and atrophic change. As a result of the double stain, some of the G cells coexpress CD99 antigen, which were more in neonate (29%) than in adult (2.6%). CONCLUSIONS: The CD99 positive cells were found in the gastric pyloric antrum during the postnatal period and progressively reduced with age. This suggests the participation of CD99 protein in the differentiation and secretory process of neuroendocrine cells.
Adult ; Antibodies ; Cell Membrane ; Cytoplasm ; Formaldehyde ; Gastric Mucosa* ; Gastrin-Secreting Cells ; Gastrins ; Humans* ; Infant ; Infant, Newborn ; Metaplasia ; Mucous Membrane ; Neuroendocrine Cells ; Neuroendocrine Tumors ; Paraffin ; Pyloric Antrum ; Secretory Pathway ; Stomach