5-Hydroxytryptamine Modulation of Rat Parotid Salivary Gland Secretion

1989 ◽  
Vol 68 (1) ◽  
pp. 59-63 ◽  
Author(s):  
W. Chernick ◽  
E. Bobyock ◽  
P. Bradford
Keyword(s):  
Salivary Glands ◽  
Salivary Secretion ◽  
Threshold Concentration ◽  
Amylase Secretion ◽  
Cell Aggregates ◽  
Salivary Gland Secretion ◽  
Combined Use ◽  
Rat Parotid

5-Hydroxytryptamine (5-HT) has been reported to produce significant responses in blowfly salivary glands, but little information is available concerning its action on mammalian salivary glands. When 5-HT (0.1 μmol/L to 10 μmol/L) is infused i. a. into anesthetized rats, no salivary secretion is obtained from either parotid or submandibular glands. However, when 5-HT is infused along with a threshold concentration of acetylcholine (0-1 mmol/L), potentiation of parotid secretory response is seen with 5-HT (1 μmol/L, 260% increase; 10 μmol/L, 146% increase). Substance P (0.3 μmol/L) combined with 5-HT (1 μmol/L) also resulted in a potentiation of parotid secretion (160% increase). Protein and calcium concentrations were not altered during such treatments. No potentiation of submandibular secretion was noted. Experiments in vitro with parotid cell aggregates exhibited no potentiation associated with the combined use of 5-HT and carbachol, as measured by amylase secretion and inositol trisphosphate accumulation. The experiments indicate that 5-HT substantially modulates parotid salivary secretion in vivo; however, the in vitro findings suggest that 5-HT does not act directly on surface glandular receptors. The magnitude of the in vivo potentiation could very well implicate circulating or released 5-HT as a physiological modulator of endogenous neurotransmitter action.

Immunolocalization of AQP-5 in rat parotid and submandibular salivary glands after stimulation or inhibition of secretion in vivo

2004 ◽  
Vol 287 (1) ◽  
pp. G151-G161 ◽  
Author(s):  
Veronika Gresz ◽  
Tae-Hwan Kwon ◽  
Hong Gong ◽  
Peter Agre ◽  
Martin C. Steward ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Salivary Glands ◽  
Salivary Secretion ◽  
Apical Plasma Membrane ◽  
Secretory Cells ◽  
Muscarinic Agonist ◽  
Rat Parotid

In vitro studies of cultured salivary gland cells and gland slices have indicated that there may be regulated translocation of aquaporin (AQP)-5 between the apical plasma membrane and intracellular compartments of the secretory cells. However, it remains unknown whether AQP-5 in salivary glands is subject to regulated trafficking in vivo. To examine this possibility, we have investigated the subcellular localization of AQP-5 in rat parotid and submandibular glands fixed in vivo under conditions of stimulated or inhibited salivary secretion. Immunofluorescence and immunoelectron microscopy was used to determine the subcellular distribution of AQP-5 in control conditions following the stimulation of secretion with pilocarpine (a muscarinic agonist) or epinephrine (an α-adrenoceptor agonist) or during inhibition of basal secretion with atropine (a muscarinic antagonist) or phentolamine (an α-adrenoceptor antagonist). Under control conditions, >90% of AQP-5 was associated with the apical plasma membrane of acinar and intercalated duct cells, with only rare gold particles associated with intracellular membrane domains. Pilocarpine treatment dramatically increased saliva production but had no discernible effect on AQP-5 distribution. However, the increased salivary secretion was associated with luminal dilation and the appearance of a markedly punctate AQP-5 labeling pattern due to clustering of AQP-5 at the microvilli (especially evident in the parotid gland) after 10 min of drug injection. No changes in the subcellular localization of AQP-5 were seen in response to epinephrine, atropine, or phentolamine treatment compared with control tissues. Thus AQP-5 is localized predominantly in the apical plasma membrane under control conditions, and neither the onset nor the cessation of secretion is associated in vivo with any significant short-term translocation of AQP-5 between intracellular structures and the apical plasma membrane.

scholarly journals THE SPIROCHETICIDAL ACTION OF PENICILLIN IN VITRO AND ITS TEMPERATURE COEFFICIENT

1944 ◽  
Vol 80 (6) ◽  
pp. 493-505 ◽  
Author(s):  
Harry Eagle ◽  
Arlyne D. Musselman
Keyword(s):  
Prolonged Exposure ◽  
Threshold Concentration ◽  
Contributing Factors ◽  
Metabolic System ◽  
Prolonged Incubation ◽  
Pathogenic Organism ◽  
Vital Functions ◽  
Combined Use

1. Penicillin was found to be actively spirocheticidal in vitro against the Reiter, Kazan, Nichols, and Noguchi strains of so called S. pallida, and a strain of mouth spirochetes. The threshold concentration was 0.01 unit per Cc. (1–160,000,000 penicillin). The rate and degree of action increased with the concentration of penicillin up to a level of approximately 0.1 to 0.25 unit per cc., which rendered more than 99 per cent of the organisms non-viable within 12 hours. Higher concentrations did not appreciably accelerate the effect. 2. Within the range 4 x 104–107 organisms per cc., the initial rate at which the spirochetes were killed was not affected by their number. Consistent with that observation, no demonstrable penicillin was bound or inactivated by thick suspensions. The amount of penicillin required to sterilize suspensions of varying density nevertheless varied to a large extent with the initial number of organisms. This was only in part due to the progressive deterioration of the penicillin with prolonged incubation; and the persistence of organisms resistant to the drug, and perhaps an adaptative change after prolonged exposure to penicillin, may be contributing factors. 3. The organisms remained actively motile for a period of 8 to 24 hours after they had been rendered non-viable by the action of penicillin. Even 500 units of penicillin per cc., or approximately 10,000 times an effectively spirocheticidal concentration, did not accelerate that delayed immobilization. It follows that, although penicillin rapidly renders the organisms non-viable, the metabolic system affected is not immediately essential to the life of the cell, and the motility and presumably other vital functions remain unaffected for a significant number of hours. 4. The rate at which the organisms were killed by penicillin increased with temperature in the range 8–40°C. With an original inoculum of 106 spirochetes per cc., the percentage of organisms surviving after 24 hours at 39–40°, 36–37°, 32–33°, 22–23°, and 8°C. was 0.02, 0.2, 1, 10, and 100 respectively; and those results were independent of the concentration of penicillin in the range 0.25 to 250 units per cc. If these observations with a non-pathogenic organism in vitro are applicable to the pathogenic organism in vivo, they suggest that the combined use of fever and penicillin in the treatment of syphilis may be more effective than either alone.

scholarly journals SOURCES OF LARVAL SALIVARY GLAND SECRETION IN THE DIPTERAN CHIRONOMUS TENTANS

1969 ◽  
Vol 40 (1) ◽  
pp. 61-78 ◽  
Author(s):  
D. Doyle ◽  
H. Laufer
Keyword(s):  
Salivary Gland ◽  
De Novo ◽  
Salivary Secretion ◽  
Disc Electrophoresis ◽  
Protein Fractions ◽  
Chironomus Tentans ◽  
Salivary Gland Secretion ◽  
Larval Salivary Gland

The soluble proteins in the hemolymph, the salivary gland, and the salivary secretion of fourth instar Chironomus tentans were examined by disc electrophoresis in acrylamide gels. Of the 11 protein fractions detected in buffered saline extracts of the gland, 10 are present also in the hemolymph. Amino acid isotope incorporation experiments indicate that the protein fractions shared by the salivary gland and the hemolymph are not synthesized in the gland but are synthesized in other larval tissues. Immunochemical studies show that most of these proteins eventually are secreted from the gland. The salivary gland in vivo and in vitro is active in de novo protein synthesis. The protein synthesized tends to form large molecular weight aggregates. As demonstrated by radioautography, at least 80% of this protein is secreted from the 30 large cells forming most of the gland. The proteins synthesized in the salivary gland cannot be detected in the hemolymph. The results of this investigation are consistent with a mechanism of secretion formation involving both de novo synthesis of some secretion proteins and the selective uptake, transport, and secretion of hemal proteins by the salivary gland.

scholarly journals In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (5) ◽  
pp. 1091-1097 ◽  
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Threshold Concentration ◽  
Current Response ◽  
Drug Induced ◽  
Inhibition Ratio ◽  
New Quinolones ◽  
The Central Nervous System ◽  
Anti Inflammatory

ABSTRACT We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

scholarly journals The Environmental Pollutant Bromophenols Interfere With Sulfotransferase That Mediates Endocrine Hormones

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhihong Dai ◽  
Furong Zhao ◽  
Ying Li ◽  
Jing Xu ◽  
Zhiyu Liu
Keyword(s):  
Competitive Inhibition ◽  
Environmental Pollutant ◽  
Threshold Concentration ◽  
Full Description ◽  
Hormone Metabolism ◽  
Endocrine Hormone ◽  
Inhibition Kinetic ◽  
New Perspective

Bromophenols (BPs), known as an important environmental contaminant, can cause endocrine disruption and other chronic toxicity. The study aimed to investigate the potential inhibitory capability of BPs on four human sulfotransferase isoforms (SULT1A1, SULT1A3, SULT1B1 and SULT1E1) and interpret how to interfere with endocrine hormone metabolism. P-nitrophenol(PNP) was utilized as a nonselective probe substrate, and recombinant SULT isoforms were utilized as the enzyme resources. PNP and its metabolite PNP-sulfate were analyzed using a UPLC-UV detecting system. SULT1A1 and SULT1B1 were demonstrated to be the most vulnerable SULT isoforms towards BPs’ inhibition. To determine the inhibition kinetics, 2,4,6-TBP and SULT1A3 were selected as the representative BPs and SULT isoform respectively. The competitive inhibition of 2,4,6-TBP on SULT1A3. The fitting equation was y=90.065x+1466.7, and the inhibition kinetic parameter (Ki) was 16.28 µM. In vitro-in vivo extrapolation (IVIVE) showed that the threshold concentration of 2,4,6-TBP to induce inhibition of SULT1A3 was 1.628 µM. In silico docking, the method utilized indicated that more hydrogen bonds formation contributed to the stronger inhibition of 3,5-DBP than 3-BP. In conclusion, our study gave the full description of the inhibition of BPs towards four SULT isoforms, which may provide a new perspective on the toxicity mechanism of BPs and further explain the interference of BPs on endocrine hormone metabolism.

scholarly journals Drug-Herb Interaction Between Selective Estrogen Receptor Modulators and Estrogenic Herbal Medicine Er-Xian Decoction in Bone in Vivo and in Vitro

2020 ◽  
Author(s):  
Ka-Ying Wong ◽  
Liping Zhou ◽  
Wenxuan Yu ◽  
Christina Chui Wa Poon ◽  
Man-Sau Wong
Keyword(s):  
Estrogen Receptor ◽  
Selective Estrogen Receptor Modulators ◽  
Serum Estradiol ◽  
Mineral Density ◽  
Alp Activity ◽  
Estrogen Receptor Modulators ◽  
Combined Use ◽  
Receptor Modulators

Abstract Background: Er-Xian decoction (EXD), a traditional Chinese Medicine for managing menopausal syndrome and osteoporosis in China, could exert osteoprotective action via activation of estrogen receptor (ERs) and regulation of serum estradiol without causing severe side effects. However, no fundamental studies have explored its potential interaction in the combined use of prescription drugs, Selective Estrogen Receptor Modulators (SERMs), regarding the osteogenic and uterotrophic effects. The present study evaluated the estrogenic effects of EXD and its potential interactions with tamoxifen and raloxifene in bone and uterus using a mature ovariectomized (OVX) Sprague-Dawley (SD) rat model and human osteoblastic MG-63 cells. Methods: Six-month-old female SD rats were randomly assigned to Sham-operated group or seven OVX groups: vehicle, 17ß-estradiol (E2, 1.0 mg/kg.day), Tamoxifen (Tamo, 1.0 mg/kg.day), Raloxifene (Ralo, 3.0 mg/kg.day), EXD (EXD, 1.6 g/kg.day), EXD+Tamoxifen (EXD+Tamo) and EXD+Raloxifene (EXD+Ralo). The effect of EXD on bodyweight, bone mineral density (BMD), bone microarchitecture, biochemical analysis of serum and urine, and uterus were evaluated. In addition, Alkaline phosphatase assay and activation of estrogen-responsive element mediated by EXD and in its combination with SERMs were investigated in MG-63 cells. Results: In vivo, EXD could interact with SERMs to modulate the serum estradiol, follicle-stimulating hormone, osteocalcin level as well as BMD and bone properties in OVX rats. Moreover, EXD could relieve the uterotrophic effect of SERMs. In vitro, EXD crude extract and EXD-treated serum could promote ALP activity. In particular, EXD-treated serum could interact with SERMs on regulating ALP activity in MG-63 cells. Conclusion: Our study demonstrated that EXD in vivo and EXD-treated serum in vitro did not weaken the osteogenic effect of SERMs. Interestingly, EXD seems to ameliorate the uterotrophic effects of SERMs. Therefore, the combined use of EXD and SERMs may be considered safe and effective in managing postmenopausal osteoporosis.

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.

Radioreceptor and biological characterization of cholecystokinin and gastrin in the chicken

1984 ◽  
Vol 246 (3) ◽  
pp. G296-G304
Author(s):  
S. R. Vigna
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Amylase Secretion ◽  
Physiological Regulation ◽  
Chicken Brain ◽  
Specific Radioimmunoassay ◽  
Cck Receptor Antagonist

Radioimmunoassay, radioreceptor assays, and bioassays were used to demonstrate that chicken brain and antrum extracts contain cholecystokinin (CCK)-like and gastrinlike peptides, respectively. C-terminal-specific radioimmunoassay of partially purified chicken CCK and gastrin gave dilution curves parallel to those of the mammalian peptides. Mouse cerebral cortical and rat pancreatic membrane radioreceptor assays were used to differentiate CCK- from gastrinlike peptides on the basis of the different CCK versus gastrin specificities of the two receptors. Confirmation of the biological activity of chicken brain CCK was obtained by stimulation of amylase secretion from rat pancreatic lobules in vitro. The specificity of this response was demonstrated by the inhibition of chicken CCK-stimulated amylase secretion by the specific CCK receptor antagonist dibutyryl cGMP. Chicken antral gastrin stimulated gastric acid secretion from the rat stomach in vivo. In contrast to previous hypotheses, it is proposed that chickens have significant amounts of an antral gastrinlike peptide and that therefore it is possible that gastrin is involved in the physiological regulation of gastric acid secretion in chickens.

Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse

2001 ◽  
Vol 281 (4) ◽  
pp. G899-G906 ◽  
Author(s):  
Robert C. De Lisle ◽  
Kathryn S. Isom ◽  
Donna Ziemer ◽  
Calvin U. Cotton
Keyword(s):  
Exocrine Pancreas ◽  
Exocrine Function ◽  
Amylase Secretion ◽  
Mrna Levels ◽  
Intestinal Function ◽  
Small Intestinal ◽  
First Time ◽  
Camp Levels

The exocrine pancreas of the cystic fibrosis (CF) mouse ( cftrm1UNC ) is only mildly affected compared with the human disease, providing a useful model to study alterations in exocrine function. The CF mouse pancreas has ∼50% of normal amylase levels and ∼200% normal Muclin levels, the major sulfated glycoprotein of the pancreas. Protein biosynthetic rates and mRNA levels for amylase were not altered in CF compared with normal mice, and increases in Muclin biosynthesis and mRNA paralleled the increased protein content. Stimulated pancreatic amylase secretion in vitro and in vivo tended to be increased in CF mice but was not statistically significant compared with normal mice. We show for the first time that the CF mouse duodenum is abnormally acidic (normal intestinal pH = 6.47 ± 0.05; CF intestinal pH = 6.15 ± 0.07) and hypothesize that this may result in increased signaling to the exocrine pancreas. There were significant increases in CF intestinal mRNA levels for secretin (310% of normal, P < 0.001) and vasoactive intestinal peptide (148% of normal, P < 0.05). Furthermore, CF pancreatic cAMP levels were 147% of normal ( P < 0.01). These data suggest that the CF pancreas may be chronically stimulated by cAMP-mediated signals, which in turn may exacerbate protein plugging in the acinar/ductal lumen, believed to be the primary cause of destruction of the pancreas in CF.

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