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At least 559 records · Page 31Linked to original sources
PubMed1987

Gastric acid secretion in the totally isolated, vascularly perfused rat stomach. A selective muscarinic-1 agent does, whereas gastrin does not, augment maximal histamine-stimulated acid secretion.

The gastric acid secretion in response to graded doses of gastrin, histamine, impromidine (a selective H2-receptor agonist), and the muscarinic-1 agonist McN-A-343 was studied in the totally isolated, vascularly perfused rat stomach. Combinations of stimulants at doses giving maximal acid secretion for each secretatogue were thereafter tested. All stimulants increased the gastric acid output significantly compared with the base-line output (7.2 +/- 2.0 mu eq/h). Gastrin induced significant increases in acid outputs at very low and physiologically relevant concentrations with a threshold concentration of 65 pM. Nevertheless, maximal gastrin-stimulated acid secretion represented only 55% of the maximal histamine-stimulated acid output of 154.8 +/- 10.0 mu eq/h. Impromidine and McN-A-343 induced a maximum 59% and 34% of maximal histamine-stimulated acid output, respectively. Adding gastrin to the maximal histamine of impromidine-stimulated stomachs did not increase the acid secretion further. Histamine and McN-A-343 in combination, however, induced a more than additive increase in the gastric acid output (232.0 +/- 14.7 mu eq/h) than did histamine and McN-A-343 separately (154.8 +/- 10.0 and 53.0 +/- 6.7 mu eq/h, respectively). The results indicate that in the rat, gastrin stimulates the parietal cell indirectly via histamine release, whereas muscarinic agents (cholinergic stimulation) act directly via a separate receptor.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed2001

Calcitonin gene-related peptide (CGRP), acting via CGRP type 1 receptors, inhibits potassium-stimulated aldosterone secretion and enhances basal catecholamine secretion from rat adrenal gland.

Calcitonin gene-related peptide (CGRP) is a potent hypotensive peptide, that acts via two main subtypes of receptors, named CGRP1 and CGRP2. CGRP belongs to a regulatory-peptide family, that includes adrenomedullin (ADM) whose aldosterone antisecretagogue and catecholamine secretagogue actions are well demonstrated. Quantitative autoradiography showed the presence of [125I]CGRP binding sites in both rat adrenal zona glomerulosa (ZG) and medulla. Binding was displaced by the CGRP1-receptor antagonist CGRP(8-37), but not by the CGRP2-receptor agonist [cys(Et)2,7]-alphaCGRP (CGRP2-A). CGRP concentration-dependently inhibited 10 mM-stimulated (but not basal) aldosterone secretion from dispersed rat ZG cells, and enhanced basal catecholamine secretion from rat adrenomedullary fragments. The responses to the maximal effective concentration of CGRP (10-8 M) were blocked by 10-7 M CGRP(8-37). CGRP2-A (10-7 M) neither altered aldosterone response to 10 mM K+ nor enhanced basal catecholamine secretion. The conclusion is drawn that CGRP, like ADM, inhibits agonist-stimulated aldosterone secretion and stimulates basal catecholamine release in the rat, exclusively acting via CGRP1 receptors.

Adrenal Glands↗
PubMed2000

Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway.

Cerebral deposits of beta-amyloid (betaA) are a major feature in Alzheimer's disease. betaA is derived from amyloid precursor protein (APP). APP is subject to N- and O-glycosylation and undergoes a series of proteolytic cleavages that lead to the release of betaA or of a non-amyloidogenic secreted form of APP (APPs). We used primary neuronal and glial cultures to investigate how cholesterol affects the production and secretion of APPs. Exposure to cholesterol for 2 h did not change the neuronal release of APPs; after 6 h APPs release was slightly lower, whereas 24 h of exposure decreased APPs in the medium by approx. 60%. The time courses were similar in astrocytes and microglia preparations. To verify whether the effect of cholesterol was a consequence of membrane rigidification we tested the activity of ganglioside GM1 and prion protein fragment PrP 106-126, which affect membrane fluidity similarly to cholesterol, on APPs secretion. Neither altered the production of APPs. APP mRNA and the total amount of APP in the cells were slightly decreased by cholesterol after 2 and 24 h respectively. Immunoblot analysis of APP associated with neuronal cells and astrocytes indicated that cholesterol progressively decreased the glycosylated forms of the protein; a similar tendency was noted in cells treated with brefeldin A and monensin, two substances that interfere with protein glycosylation. The cell-surface biotinylation method showed that in cholesterol-treated cells APP reached the plasma membrane. Our results indicate that cholesterol decreases the secretion of APPs by interfering with APP maturation and inhibiting glycosylation of the protein; although APP is inserted in the membrane it is not cleaved by alpha-secretase.

Amyloid beta-Protein Precursor↗
PubMed1979

Murine plasma cells secreting more than one class of immunoglobulin. VI. Secretion of completely assembled IgG2b and IgA molecules with segregated heavy chains and free light chains by spontaneous myeloma SAMM 368 in culture.

The antigenic and molecular characteristics of the two immunoglobulins secreted by a single cell line of plasmacytoma SAMM 368 were analyzed by polyacrylamide gel electrophoresis of biosynthesized proteins. Adapted to continuous in vitro cultivation, this BALB/c plasmacytoma secretes at least 98% of its heavy chains as components of fully assembled and isotypically uniform IgG2b and IgA molecules. The IgA is secreted as monomers, dimers, and multimers with chemical properties typical of BALB/c myeloma IgA including disulfide bonded J chain and noncovalently bonded light chains. The noncovalently bonded light chains are monomers rather than dimers. Free light chains are also secreted. The ability to segregate heavy chains is attributed either to chemical, enzymatic, or compartmental regulatory factors operating within these plasma cells.

Animals↗
PubMed2002

[Changes in the cytological analysis of nasal secretions during a nasal secretion].

Changes of cytological parameters in the course of the nasal provocative test (NPT) we studied in 30 patients aged 14-43 years with chronic rhinitis of unknown etiology. Solutions of allergens in various concentrations were used for NPT and skin testing. NPT results were estimated clinically according to four-point scale and rhinocytogram 20 minutes after injection of different concentrations of allergens to nasal cavity. The results of the provocative tests coincide with case history data more frequently than skin test results. The discrepancy between anamnesis and results of skin tests in the group of patients reached 30.7%. A mean 8-fold increase in eosinophil count in nasal secretion was observed in patients with clinically confirmed NPT (76% cases) 20 minutes after injection of a minimal concentration of allergen extract to the nasal cavity. This eosinophil infiltration of nasal secretion preceded the occurrence of clinical symptoms. An unusual cytological picture of nasal secretion was observed in three patients with positive anamnestic data, results of skin testing and NPT. Eosinophil infiltration of nasal recreation was absent but neutrophil number increased. Increased eosinophil count on rhinocytogram after injection of allergen extract to nasal cavity can serve as an objective criterion of NPT. The described cases of neutrophil infiltration of nasal secretion testify to possible participation of these cells in acute allergic inflammation in patients with clinically positive NPT.

Humans↗
PubMed2003

Inhibition of hormone secretion in GH-secreting pituitary adenomas by receptor-subtype specific somatostatin analogues in vitro.

The aim of the study was to determine the inhibitory effects of somatostatin analogues with relative specificity to somatostatin receptor subtype 2 (SSTR2) (BIM-23197), subtype 5 (SSTR5) (BIM-23268), and their combination on GH and PRL secretion in acromegalic adenomas in vitro. Three types of answer were observed: 1. In one resistant adenoma no inhibition was achieved. 2. The GH secretion in six adenomas was suppressed significantly more (p < 0.01 or p < 0.001 using Mann-Whitney U-test in concentration range of 10(-12) to 10(-8) mol/l) with SSTR2 specific analogue BIM-23197 with no additive effect of compounds combination. 3. In three adenomas the potency of BIM-23197 and BIM-23268 was almost equal and the combination of these SSTR2 and SSTR5 specific compounds had statistically significant additive effect (p < 0.05 or p < 0.01 in concentration range of 10(-12) to 10(-8) mol/l). PRL secretion of five adenomas was more suppressed with SSTR5 specific BIM-23268 (statistically significant in concentrations 10(-10) to 10(-8) mol/l). In conclusion the somatostatin analogue BIM-23268 had an additive effect on suppression of GH secretion in a subset of adenomas, where both SSTR2 and SSTR5 were involved. This effect was not observed in the majority of tumours, where the inhibitory effect seems to be mediated via SSTR2 only.

Acromegaly↗
PubMedDate not supplied

An investigation of the requirement for increased LH secretion during the compensatory response in androgen secretion after unilateral castration of the adult rat.

The endocrine mechanisms underlying the response to unilateral castration were examined by determining systemic androgen and luteinizing hormone (LH) concentrations, as well as testicular vein androgen at 3, 6, 12, and 24 hours after sham surgery and castration. Systemic androgen was significantly depressed 3 hours after unilateral castration, but had recovered to concentrations observed in sham operated rats at 6, 12, and 24 hours. The recovery of serum androgen after castration was apparently due to increased testicular secretion of androgen, seen as a significant increase in testicular vein androgen. Systemic concentrations of bioactive and immunoactive LH were significantly increased only at 6 hours after castration. The authors next examined whether the increase in LH was necessary for the compensatory secretion of androgen seen after castration. This was accomplished by examining the response to castration when circulating LH was prevented from changing by suppressing endogenous LH secretion with subcutaneous steroid implants and maintaining circulating LH with subcutaneous osmotic pumps containing ovine LH. The compensatory increase in testicular vein androgen was observed 1 and 7 days after castration in rats bearing sham implants. When circulating LH was prevented from changing by using the combination of steroids and LH, however, compensatory secretion of androgen did not occur 1 and 7 days after castration.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1991

Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line.

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.

Adenosine↗
PubMed1989

[Role of cyclic AMP in gastric secretion. The secretion and mechanism of action of gastrin].

The present study involved evaluation of the role played by cyclic AMP on the secretion and mechanism of action of gastrin in man. On the basis of the results obtained, gastrin secretion induced by an excessive rise in gastric pH is accompanied by a simultaneous increase in plasma cyclic AMP concentrations (p less than 0.05) as well as a tissue cyclic AMP in the region of the fundus (p less than 0.001). By contrast, no significant change was seen regarding antropyloric AMP. As a result, it is felt that cyclic AMP does not play a direct role in the secretion of gastrin by G cells but is a mediator of the mechanism of action of gastrin in terms of the secretion of HCl by the parietal cell.

Cyclic AMP↗
PubMed1989

SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages.

We have reported that SV40-transformed human lung fibroblasts secrete a 92-kDa metalloprotease which is not detectable in the parental cell line IMR-90. We now present the complete structure of this enzyme along with the evidence that it is identical to the 92-kDa metalloprotease secreted by normal human alveolar macrophages, phorbol ester-differentiated monocytic leukemia U937 cells, fibrosarcoma HT1080 cells, and cultured human keratinocytes. A similar, perhaps identical, enzyme can be released by polymorphonuclear cells. The preproenzyme is synthesized as a polypeptide of predicted Mr 78,426 containing a 19 amino-acid-long signal peptide and secreted as a single 92,000 glycosylated proenzyme. The purified proenzyme complexes noncovalently with the tissue inhibitor of metalloproteases (TIMP) and can be activated by organomercurials. Activation with phenylmercuric chloride results in removal of 73 amino acids from the NH2 terminus of the proenzyme, yielding an active form capable of digesting native types IV and V collagen. The in vitro substrate specificity of the enzyme using these substrates was indistinguishable from that of the 72-kDa type IV collagenase. The 92-kDa type IV collagenase consists of five domains; the amino-terminal and zinc-binding domains shared by all members of the secreted metalloprotease gene family, the collagen-binding fibronectin-like domain also present in the 72-kDa type IV collagenase, a carboxyl-terminal hemopexin-like domain shared by all known enzymes of this family with the exception of PUMP-1, and a unique 54-amino-acid-long proline-rich domain homologous to the alpha 2 chain of type V collagen.

Amino Acid Sequence↗
PubMed1989

Protease secretion by Erwinia chrysanthemi. Proteases B and C are synthesized and secreted as zymogens without a signal peptide.

The gene encoding the secreted 53-kDa metalloprotease (protease B) and the 5' end of the gene encoding the secreted 55-kDa metalloprotease (protease C) of the Gram-negative bacterium Erwinia chrysanthemi have been sequenced. The predicted sequences of the two proteases do not have typical signal sequences at their NH2 termini. Both proteases are synthesized as inactive higher molecular weight precursors (zymogens proB and proC) which are secreted into the external medium where divalent cation-mediated activation occurs. The activation of proB occurs with a t1/2 of less than 5 min at 37 degrees C in Luria broth medium, whereas that of proC occurs with a t1/2 of about 150 min. The NH2 termini of purified proteases B, proB, and C were sequenced. ProB starts at the initiator methionine whereas B and C start, respectively, at residues +16 and +18 of the sequence deduced from the nucleotide sequence. A short NH2-terminal extension is therefore removed during the activation process, most likely by an autocatalytic mechanism. Protease B shows a high degree of sequence homology with the secreted 50-kDa metalloprotease of Serratia marcescens, which also lacks a signal peptide and for which an inactive higher molecular weight form has been reported.

Amino Acid Sequence↗
PubMed1987

Secreted proteins from normal and SV40 transformed human MRC-5 fibroblasts: toward establishing a database of human secreted proteins.

Analysis by means of computerized two-dimensional gel electrophoresis (NEPHGE, IEF) of the [35S]-methionine labeled proteins secreted by normal human MRC-5 fibroblasts revealed 476 polypeptides (258 acidic and 218 basic), many of which appeared as charge trains due to modification. Similar analysis of the proteins secreted by SV40 transformed MRC-5 fibroblasts (MRC-5 V2) showed a striking decrease in the levels of many of these proteins as well as the appearance (or increased synthesis) of 47 polypeptides that were either absent or present in very low amounts in normal cells. Of the major secreted polypeptides whose relative proportion decreased dramatically in the MRC-5 V2 cells, 15 were found to be abundant components of other normal (nontransformed) fibroblasts (W138, Xeroderma pigmentosum cell lines). Low levels of these radioactively labeled polypeptides were observed in transformed human cell lines of fibroblast (W138, SV40, HT1080), epithelial (HeLa, transformed amnion cells (AMA), A431, A459) and myeloid (HL-60) origin. No major secreted polypeptide from MRC-5 V2 cells was synthesized exclusively by the transformed cell lines.

Cell Line, Transformed↗
PubMed1987

Heterogeneity among T helper cells. Interleukin 2 secretion and help for immunoglobulin secretion.

T lymphocytes are thought to provide "help" for B cells by activating them from the resting state, by secretion of antigen-nonspecific lymphokines that promote B cell differentiation and maturation, and by providing signals that induce isotype switching. To clarify the extent to which these different forms of helper activity could be carried out by individual T cells, we set up cultures in which B cells activated, and were in turn themselves stimulated by, limiting numbers of T cells through differences at the H-2 or Mls loci. At T cell doses at which responses were likely to represent the activity of individual helper T cells (or their immediate clonal progeny), we found that some T cells were able both to produce interleukin 2 (IL-2) and to induce secretion of both IgM and IgG, whereas others induced immunoglobulin (Ig) secretion without detectable IL-2 production, and still others made IL-2 but did not promote antibody secretion. We could not detect B cell stimulatory factor 1 production by alloantigen-stimulated T cells, and the addition of antibodies to B cell stimulatory factor 1 did not prevent Ig production. Two results, however--higher Ig accumulation in those wells that received an IL-2-producing cell, and inhibition by anti-IL-2 receptor antibodies of B cell but not T cell function--are consistent with a direct stimulatory effect of IL-2 on B cells in this system. The pattern of helper functions exhibited by T cells freshly isolated from mice differs from that inferred from studies of cloned lines of T cells in long term cultures.

Animals↗
PubMed1986

Human duodenal mucosal bicarbonate secretion. Evidence for basal secretion and stimulation by hydrochloric acid and a synthetic prostaglandin E1 analogue.

The factors responsible for prevention of duodenal mucosal injury are not known. This series of experiments was performed to determine whether the human duodenum secretes bicarbonate that could prevent mucosal damage. To isolate a 4-cm segment of proximal (i.e., the duodenal bulb) or distal duodenum free of contamination from either gastric or pancreaticobiliary secretion, or both, methods were developed using occlusive balloons. The test segment was perfused with NaCl (2 ml/min, 37 degrees C) containing [14C]PEG as a nonabsorbable marker, and bicarbonate output was quantitated. Mean (+/- SE) basal proximal duodenal bicarbonate output was 143 +/- 17 mumol/cm X h. A 5-min infusion of 25, 50, and 100 mM HCl directly into the isolated proximal duodenal test segment increased bicarbonate output to 167 +/- 29, 199 +/- 19, and 278 +/- 49 mumol/cm X h, respectively, during the hour after acidification. Distal duodenal acidification (25, 50, and 100 mM) also increased bicarbonate output from the isolated proximal duodenal test segment. A synthetic prostaglandin E1 analogue, misoprostol (1.67-13.3 micrograms/min), infused directly into proximal or distal test segments significantly stimulated bicarbonate outbreak; peak responses were 644 +/- 35 mumol/cm X h and 171 +/- 20 mumol/cm X h (p less than 0.001), respectively. Thus, in humans, the proximal and distal duodenal mucosa secretes bicarbonate at rest; direct acidification of the proximal duodenum stimulates bicarbonate output; acidification of the distal duodenum beyond the isolated test segment also increased proximal duodenal bicarbonate output; and a synthetic prostaglandin E1 analogue stimulated both proximal and distal bicarbonate output; however, distal duodenal bicarbonate output was significantly less, indicating a proximal-to-distal gradient in bicarbonate secretion.

Adult↗
PubMed1988

[Comparative studies of bronchial secretion in children with chronic, nontuberculous lung diseases. 1. Methodico-technical studies of secretion collection and interpretation of the results].

The aim of the present study was to estimate different proteins in 166 bronchial secretions from 63 children with chronic nontuberculous lung diseases. In a first publication some methodological problems as the age of patients, the position of the bronchoscope, the bronchoscopic and bronchographic situation resp. and the mode of extraction are analysed. With increasing age the concentration of sIgA is elevated - in contrast to the IgG concentration. Only in severe diseases albumin declines with increasing age. Some variations in the concentration of proteins have been observed in relation to the position of the bronchoscope and in regard to a repeated extraction of bronchial secretions. No important differences in the concentration of proteins have been found in secretions obtained during diverse days. The different protein patterns in the bronchial secretions could be explained only partly by variations in the course of diseases.

Adolescent↗
PubMed1977

[Cells secreting antibodies originate from cells secreting immunoglobulins without a detectable antibody function for the antigen injected].

Cells secreting immunoglobulins without detectable antibody function arising after an injection of horseradish peroxidase were micromanipulated from the center of haemolytic plaques of Sheep red blood cells coated with anti-Ig antibodies. These cells were cultured individually for 48 hrs, with irradiated cells as feeder layer and in the presence of the immunogen and of LPS. It was shown that after this time 22% of the immunoglobulin-secreting cells had generated antiperoxidase antibody-secreting cells or were transformed into antibody-secreting cells.

Animals↗
PubMed1993

Differential transforming abilities of non-secreted and secreted forms of human fibroblast growth factor-1.

Fibroblast growth factor (FGF)-1(1-154), the precursor for acidic FGF-1(21-154), is a potent angiogenic polypeptide, the structure of which lacks a signal peptide sequence for secretion. To investigate the biological significance of this structural feature, we have attempted forced secretion of FGF-1 through fusion of the entire FGF-1 coding frame with the signal peptide (sp) from the hst/KS3 gene, a secretory member of the heparin-binding growth factor family. We also studied the transforming ability of the signal-less forms of FGF-1 comprising FGF(1-154) and FGF-1(21-154). The presence of a soluble and biologically active form of FGF-1 was readily detected in the conditioned medium of NIH 3T3 cells transfected with sp-hst/KS3:FGF-1(1-154) as demonstrated by Western blot analysis and DNA synthesis assays, whereas sp-hst/KS3:FGF-1(21-154) was not detectable in conditioned medium even though the protein was detected in cellular extracts. The secreted form of sp-hst/KS3:FGF-1(1-154) stimulated the proliferation of human umbilical vein endothelial cells in vitro and was able to induce receptor-mediated tyrosine phosphorylation. Furthermore, the forced secretion of biologically active FGF-1 resulted in NIH 3T3 cell transformation as demonstrated by altered morphology in vitro, the formation of discrete colonies in soft agarose, growth under serum-free conditions, and ability to rapidly form highly vascular tumors in vivo. Interestingly, sp-hst/KS3:FGF-1(21-154) also mediated the transition to a transformed phenotype despite the inability to detect extracellular FGF-1 in the media conditioned by these NIH 3T3 cell transfectants. Although the transfection of FGF-1(21-154) yielded similar NIH 3T3 cell morphologic changes, these transfectants did not grow under serum-free conditions or yield colonies in soft agarose, and formed tumors in vivo with delayed kinetics. Furthermore, the FGF-1(1-154) NIH 3T3 cell transfectants did not exhibit morphologic changes, and this may be due to the inability of mRNA to express protein. These data suggest that although non-sp forms of FGF-1 may alter the monolayer phenotype of NIH 3T3 cells in vitro, the ability of FGF-1 to transform NIH 3T3 cells requires the function of a sp-directed secretory pathway and suggests that this pathway increases tumorigenicity in vivo.

3T3 Cells↗
PubMed1994

Synthesis and secretion of bacterial antigens by attenuated Salmonella via the Escherichia coli hemolysin secretion system.

We describe a plasmid system which allows the secretion of foreign antigens in attenuated Salmonella aroA strains by the secretion apparatus of E. coli hemolysin. The gene (or gene fragment) encoding the antigen is inserted in frame into a residual position of the hlyA gene, encoding the HlyA secretion signal (HlyAs). Generally, the fused gene is efficiently expressed and the synthesized antigen is in part secreted into the culture supernatant and in part exposed on the surface of the producing Salmonella strain. The successful use of this approach is demonstrated with two antigens of Salmonella typhimurium, PagC and SlyA, both of which are potent virulence factors but produced only in small amounts under in vitro culture conditions and two virulence proteins of Listeria monocytogenes, p60 and listeriolysin. Interestingly the listeriolysin fusion protein proved to be cytolytically active and allowed, when expressed in Salmonella, the escape of these bacteria into the cytoplasm of infected macrophages.

Antigens, Bacterial↗