Calcium Signaling in Salivary Secretion

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.

Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population

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.

Prueba de basculación (Tilt Table Testing): Comparación de dos protocolos: isoproterenol versus nitroglicerina / Comparison of the use of isoproterenol or nitroglycerine during the Tilt test

Background: There is debate about the advantages of different protocols usefulness of tilt test for the diagnosis of vasovagal collapse. Aim: To compare the sensitivity, specificity, adverse reactions, complications and time requirements of two different Tilt test protocols. Material and Methods: A Tilt test using isoproterenol in progressive doses (2 μg for 10 min and 5 μg for 5 min posteriorly was performed in 159 patients aged 9 to 84 years (59 males). Another Tilt test using sublingual nitroglycerine in doses of 0.3 mg was performed in 201 patients aged 8 to 87 years (62 males). Also, 20 healthy volunteers were tested. Results: The positivity rates of the tests using isoproterenol and nitroglycerin were 75.5 and 77.6% respectively (NS). The figures for sensitivity were 98.4 and 99.3% (NS). The figures for specificity were 93.2 and 98.4% (NS). The test using isoproterenol requires 15 more minutes. As adverse reactions, 38% of participants experienced palpitations with isoproterenol and 22% experienced headache with nitroglycerin. Conclusions: The Tilt test with nitroglycerin is shorter, simpler, painless, with less personnel involved and has the same diagnostic accuracy than the test with isoproterenol.

Sortin2 enhances endocytic trafficking towards the vacuole in Saccharomyces cerevisiae

BACKGROUND: A highly regulated trafficking of cargo vesicles in eukaryotes performs protein delivery to a variety of cellular compartments of endomembrane system. The two main routes, the secretory and the endocytic pathways have pivotal functions in uni- and multi-cellular organisms. Protein delivery and targeting includes cargo recognition, vesicle formation and fusion. Developing new tools to modulate protein trafficking allows better understanding the endomembrane system mechanisms and their regulation. The compound Sortin2 has been described as a protein trafficking modulator affecting targeting of the vacuolar protein carboxypeptidase Y (CPY), triggering its secretion in Saccharomyces cerevisiae. RESULTS: A reverse chemical-genetics approach was used to identify key proteins for Sortin2 bioactivity. A genome-wide Sortin2 resistance screen revealed six yeast deletion mutants that do not secrete CPY when grown at Sortin2 condition where the parental strain does: met18, sla1, clc1, dfg10, dpl1 and yjl175w. Integrating mutant phenotype and gene ontology annotation of the corresponding genes and their interactome pointed towards a high representation of genes involved in the endocytic process. In wild type yeast endocytosis towards the vacuole was faster in presence of Sortin2, which further validates the data of the genome-wide screen. This effect of Sortin2 depends on structural features of the molecule, suggesting compound specificity. Sortin2 did not affect endocytic trafficking in Sortin2-resistant mutants, strongly suggesting that the Sortin2 effects on the secretory and endocytic pathways are linked. CONCLUSIONS: Overall, the results reveal that Sortin2 enhances the endocytic transport pathway in Saccharomyces cerevisiae. This cellular effect is most likely at the level where secretory and endocytic pathways are merged. Them Sortin2 specificity over the endomembrane system places it as a powerful biological modulator for cell biology.

Emerging Hyperprolactinemic Galactorrhea in Obsessive Compulsive Disorder with a Stable Dose of Fluoxetine

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.

From endoplasmic reticulum to Golgi apparatus: a secretory pathway controlled by signal molecules / 浙江大学学报·医学版

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.

Physiology of Lactation / 한양의대학술지

To produce milk, four secretory processes are synchronized in the alveolar cell of the mature, functional mammary gland: (1) exocytosis, (2) fat synthesis and secretion, (3) secretion of ions and water, and (4) transcytosis of immunoglubulins and other substances from the interstitial space. Milk is synthesized continuously into the alveolar lumen, where it is stored until milk removal from the breast is initiated. Prolactin mediates the central nervous system regulation of milk secretion, but its influence is modified greatly by local factors that depend on milk removal from the breast. Oxytocin mediates milk let-down by stimulating the contraction of myoepithelial cells that surround the alveoli and ducts. Lactogenesis includes all the processes necessary to go from the undifferentiated mammary gland in the early pregnant animal to full lactation sometime after parturition. The most important factors in initiation of lactogenesis stage II appear to be progesterone withdrawal. The metabolic demands of breastfeeding require an increase in maternal metabolism. Postpartum suppression of fertility is thought to be the result of an alteration in pulsatile gonadotropin releasing hormone secretion from the hypothalamus. Women who wish to ensure against pregnancy during lactation usually are advised to use other contraceptive means.

Central administration of Orphanin FQ inhibits GnRH secretion by ORL1 receptor in the median eminence of freely moving ovariectomized rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>This study aimed to investigate the possible role of Orphanin FQ (OFQ) in the regulation of hypo-thalamic gonadotropin-releasing hormone (GnRH) secretion.</p><p><b>METHODS</b>The method of push-pull perfusion and radioimmuno-assay (RIA) were adopted to examine the secretory profile of GnRH in the median eminence (ME) in freely moving ovari-ectomized (OVX) rats after intracerebroventricular (icv) injection of OFQ and/or [Nphe(1)]NC(1-13)NH(2) (NC13), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor).</p><p><b>RESULTS</b>GnRH release from ME significantly decreased from 40 min to 80 min after the administration of 20 and 200 nmol OFQ in OVX rats (P < 0.05). This inhibitory effect of 20 nmol OFQ could be abolished by pretreatment with equal dose of NC13. More interestingly, GnRH secretion from ME was increased markedly 60 min after icv injection of 100 and 200 nmol NC13 (P < 0.05).</p><p><b>CONCLUSION</b>Our results suggested central administration of OFQ could inhibit the release of GnRH in the ME of hypothalamus through ORL1 receptor, providing further in vivo evidence supporting the role of OFQ in the control of GnRH secretion.</p>

The significance of pre-S1 mutants as a cause of groundglass hepatocyte during HBV infection / 대한내과학회지

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.

Ca2 -activated K Currents of Pancreatic Duct Cells in Guinea-pig

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.

Significance of CD99 Immunoreactive Cells in relation to Gastrin-producing Cells in Human Gastric Mucosa

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.

Inhibitory Effect of Cortex mori on the Colchicine-induced Mast Cell Activation / 대한해부학회지

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.

Ca2+-dependent exocytosis in endocine, exocrine, and nonsecretory cells

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.

Morphological Characteristics of the Atrium as an Endocrine Organ: I. Luminal Structure of Atria in Various Animals Using Corrosion Casting Method / 체질인류학회지

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.