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S Kawauchi

Publications and source records attributed to S Kawauchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Isolation, characterization, and expression analysis of zebrafish large Mafs.

Large Maf proteins, which are members of the basic leucine zipper (b-Zip) superfamily, are involved in the determination and control of cellular differentiation. The expression patterns of various vertebrate large Maf mRNAs were described previously. Here, we report the cloning of a novel zebrafish large Maf cDNA, SMaf1 (Somite Maf1), and other zebrafish large Mafs, the N-terminus domains of which possess transactivational activity. We also analyzed the expression patterns of SMaf1 and SMaf2 (Somite Maf2)/Krml2 as well as MafB/Val and c-Maf during zebrafish embryogenesis. In particular, the robust expression of the novel SMaf1 mRNA, which overlapped that of MyoD, in somitic cells during somitogenesis was noteworthy. In addition, the expression patterns of SMaf2 and MafB in the blood-forming regions, and those of c-Maf and MafB in the lens cells showed spatial redundancy, although the temporal appearance of these genes at these sites differed. These data indicate that SMafs may play important roles in somitogenesis, and that Maf proteins may have overlapping and yet specific functions as to the determination and differentiation of cell lineages.

Amino Acid Sequence↗
PubMed2001

DNA sequence copy number aberrations associated with histological subtypes and DNA ploidy in gastric carcinoma.

We have analyzed DNA sequence copy number aberrations (DSCNAs) and DNA ploidy by using comparative genomic hybridization and laser scanning cytometer in gastric carcinomas (GCs) to elucidate the genomic aberrations in relation to clinicopathological parameters. Thirty-two out of 33 cases showed one or more DSCNAs with a mean number of 11.7 per tumor. High-level gains were detected at 2p, 3q, 6p, 7p, 7q, 8q, 12p, 13q, 19q, and 20q. Frequency of gross genomic abnormalities and chromosome regions that have genomic aberrations were similar in both intestinal- and diffuse-type GCs, except aberrations at 8p, 9p, 12q, and 20q. The overall number of DSCNAs was significantly greater in DNA aneuploid tumors than that in DNA diploid tumors. We detected genomic aberrations characterized by histological subtype, tumor location, and DNA ploidy status: gain of 20q and losses of 8p and 9p in intestinal-type GCs, gains of 8p and 12q in diffuse-type GCs, gain of 20q in the lower third GCs, and loss of 5q, 9p, 10q, 16q, and 18q in DNA aneuploid GCs. Furthermore, 5q loss is associated with DNA aneuploidy (P = 0.0001) or the total number of losses (P = 0.001), gain + losses (P = 0.004), and high-level gains (P = 0.001) in GCs. Among these loci, chromosome 8p was unique. Gain of 8p was more common in diffuse-type GC, whereas loss of 8p was more frequently detected in intestinal-type GC. In conclusion, we describe chromosomal regions of 5q, 8p, and 20q, which are of interest for further investigation of GCs.

Adenocarcinoma↗
PubMed2001

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

Aged↗
PubMed2001

Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro.

We examined the effect of NO on acid secretion in vitro using isolated preparations of Bullfrog stomach. The bullfrog fundic mucosa was bathed in unbuffered Ringer solution gassed with 100% O2 on the mucosal side and HCO3- Ringer's solution gassed with 95% O2/5% CO2 on the serosal side, and the acid secretion was measured at pH 5.0 using the pH-stat method and by adding 5 mM NaOH. Serosal addition of a NO donor NOR-3 (10(-5) approximately 10(-3) M: (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine) caused an increase of acid secretion in a dose-dependent manner, the effect lasting about 1 hr and reaching a maximal level of 2-fold the basal values. The acid stimulatory effect of NOR-3 was mimicked by another NO donor SNAP (10(-3) mol/L: S-nitroso-O-N-acetyl-penicillamine) and markedly and markedly inhibited by prior administration of cimetidine (10(-5) mol/L) as well as compound 48/80 (the mast cell degranulator). Likewise, the increased acid response to NOR-3 was significantly mitigatd by pretreatment with carboxy-PTIO (a NO scavenger) or superoxide dismutase (SOD), but not by indomethacin or methylene blue (a guanylyl cyclase inhibitor). Neoither L-NAME, L-arginine nor dibutyryl guanosine-3',5'-cyclic monophosphate (dbcGMP) has any effect on the basal acid secretion. Serosal addition of NOR-3 caused a significant increase in the luminal release of histamine, and this response was inhibited by pretreatment with either compound 48/80, carboxy-PTIO or SOD. These results suggest that the NO donor increases gastric acid secretion in the isolated frog stomach in vitro, and this action is mediated by endogenous histamine released from mast cells, the process being cGMP-independent but requiring the presence of superoxide radicals. In addition, it was speculated that the histamine releasing action of NO may be due to peroxynitrite produced by NO and superoxide radicals.

Animals↗
PubMed2000

Aldehyde dehydrogenase 6, a cytosolic retinaldehyde dehydrogenase prominently expressed in sensory neuroepithelia during development.

We have isolated the chick and mouse homologs of human aldehyde dehydrogenase 6 (ALDH6) that encode a third cytosolic retinaldehyde-specific aldehyde dehydrogenase. In both chick and mouse embryos, strong expression is observed in the sensory neuroepithelia of the head. In situ hybridization analysis in chick shows compartmentalized expression primarily in the ventral retina, olfactory epithelium, and otic vesicle; additional sites of expression include the isthmus, Rathke's pouch, posterior spinal cord interneurons, and developing limbs. Recombinant chick ALDH6 has a K(0.5) = 0.26 microm, V(max) = 48.4 nmol/min/mg and exhibits strong positive cooperativity (H = 1.9) toward all-trans-retinaldehyde; mouse ALDH6 has similar kinetic parameters. Expression constructs can confer 1000-fold increased sensitivity to retinoic acid receptor-dependent signaling from retinol in transient transfections experiments. The localization of ALDH6 to the developing sensory neuroepithelia of the eye, nose, and ear and discreet sites within the CNS suggests a role for RA signaling during primary neurogenesis at these sites.

Acyclic Monoterpenes↗
PubMed2000

Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act quite specifically on human immunodeficiency virus type 1 (HIV-1). In general, they are not effective on human immunodeficiency virus type 2 (HIV-2) or simian immunodeficiency virus (SIV). Only SIV strains from African green monkeys are sensitive to several NNRTIs. Here we isolated NNRTI- and 3TC-resistant SIVagm variants. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. The roles of the observed mutations in NNRTI-resistance of SIVagm and HIV-1 were further confirmed by site-directed mutagenesis. The present results have provided a new insight into the common mechanism of sensitivity of HIV- 1 and SIVagm to NNRTIs.

Amino Acid Sequence↗
PubMed2000

The development of a cell array and its combination with laser-scanning cytometry allows a high-throughput analysis of nuclear DNA content.

We developed a cell array device for analyzing cellular characteristics such as DNA ploidy, numerical chromosomal aberrations, and antigen expression in multiple specimens in a single experiment. Fifty (10 x 5) spots, 2 mm in diameter, were arrayed in an area of 30 x 16 mm on a glass slide, and approximately 1,000 cells were placed on each spot. To demonstrate the usefulness of the cell array, we measured nuclear DNA content using laser-scanning cytometry for DNA ploidy analysis in nine human tumor cell lines and normal lymphocytes. Combining the cell array with laser-scanning cytometry allows not only measurement of nuclear DNA content for 50 samples but also easy comparison of DNA ploidy among the samples in a single experiment. In addition, we used the cell array for fluorescence in situ hybridization using a DNA probe specific for the pericentromeric region of chromosome 11.

Cell Count↗
PubMed2000

Infrared and XAFS study on structure and transition behavior of zinc stearate.

Structure and transition behavior of zinc(II) stearate crystal were investigated by infrared and XAFS spectroscopies. Structure of zinc stearate at room temperature was estimated as follows. From XAFS analysis, the coordination number of the carboxylate groups around the zinc atom was evaluated as 4 and the Zn-O distance as 1.95 A. Based on the infrared spectrum and a normal mode analysis, the conformation of the alkyl chain was confirmed as all-trans and the sub-cell packing was considered as parallel type, and also the coordination form of the carboxylate groups was determined as bridging bidentate type. As increasing temperature, zinc stearate has a solid liquid phase transition at 130 degrees C. At the transition, the alkyl chains goes into liquid like state as reported by Mesubi but the coordination structure was confirmed to be maintained.

Molecular Conformation↗
PubMed2000

Prognostic significance of apoptosis in synovial sarcoma: correlation with clinicopathologic parameters, cell proliferative activity, and expression of apoptosis-related proteins.

bcl-2 overexpression in synovial sarcomas has been recently reported. Although it is widely known that bcl-2 suppresses apoptosis in various cells, there are no studies that have examined the significance of apoptosis in synovial sarcoma. In the present study, we visualized apoptotic tumor cells by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end-labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of apoptosis was analyzed in relation to several clinicopathologic parameters, cell proliferative activity, and immunohistochemical expression of apoptosis-related proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index (MI) (ñ = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (ñ = 0.52, P = 0.0005). There was a highly significant association between high TUNEL-I value (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and were negative or only sporadically positive for Fas, Fas ligand, p53, and p21 (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in primary synovial sarcoma was considered to be an indicator of poor prognosis. In addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis-regulating mechanisms, including the bcl-2 family.

Adolescent↗
PubMed2000

Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma.

Forty-nine cases of synovial sarcoma were evaluated for mutation of the p53 gene, amplification of the MDM2 gene and mutation of the H-ras gene, and for the relation of these factors to overall survival and clinicopathologic parameters. All investigations were carried out on formalin-fixed paraffin-embedded materials. Furthermore, we evaluated the expression of p53 protein, MDM2, and p21(WAF1/CIP1) immunohistochemically in these cases, together with an assessment of proliferative activities using monoclonal antibody MIB-1. Nine of the 49 cases (18.4%) had p53 gene alteration detected by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. Eleven cases (24%) showed nuclear accumulation of p53 protein in more than 10% of the tumor cells. Among them, only three cases contained gene mutations. There was no correlation between p53 nuclear accumulation and p53 gene alteration. MDM2 gene amplification, as shown by differential PCR, was observed in 19 out of 47 cases (40%). Nineteen out of 49 cases (38.8%) showed immunoreactivity for MDM2. MDM2 gene amplification and the expression of MDM2 protein showed a significant positive relationship (P = 0.0004). Moreover, MDM2 immunoreaction was significantly correlated with nuclear accumulation of p53 protein (P = 0.023). Positive immunoreaction for p21(WAF1/CIP1) was observed in 21 out of 48 cases (43.8%). p21(WAF1/CIP1) expression was correlated with p53 protein expression. H-ras gene mutations were seen in only three cases (6.1%). All mutations were in codon 12 (one GGC-to-AGC [Gly-to-Ser] mutation and two GGC-to-GAC [Gly-to-Ap] mutations). The gene alteration of p53, MDM2, and H-ras did not affect the patients' prognosis. Although the cases with positive immunoreaction for p53 tended to have a worse prognosis, the difference was not statistically significant (P = 0.13). No correlation was observed between MIB-1 LI and the immunohistochemical expression of p53, MDM2, and p21(WAF1/CIP1) or the mutation status of p53 and H-ras. On the other hand, high MIB-1 LI (more than 10) significantly correlated with poor prognosis (P < 0.0001). Our results suggest that p53 gene mutation does not appear to be a major prognostic factor and H-ras mutations are infrequent in synovial sarcoma.

Adolescent↗
PubMed2000

Interactive roles of endogenous prostaglandin and nitric oxide in regulation of acid secretion by damaged rat stomachs.

BACKGROUND: The acid inhibitory mechanism in the damaged stomach is known to involve endogenous nitric oxide (NO) as well as prostaglandin (PG). AIM: To investigate the interaction between PG and NO in regulation of acid secretion in the stomach following damage. METHODS: Under urethane anaesthesia, a rat stomach was mounted in an ex vivo chamber and perfused with saline. Acid secretion, luminal PGE2, NO metabolites (NOx) and histamine output were measured before and after application of 20 mM taurocholate Na (TC) for 30 min, with or without pre-treatment with indomethacin and/or N(G)-nitro-L-arginine methyl ester (L-NAME). RESULTS: Exposure of the stomach to TC caused a decrease in acid secretion, with concomitant increase of both luminal NOx and PGE2. Either L-NAME or indomethacin reduced the decrease in acid secretion in response to TC, but only L-NAME allowed acid secretion to increase over basal values. L-NAME prevented the increase of luminal NOx after TC treatment, while indomethacin inhibited PGE2 release during and after exposure to TC. The increase in acid secretion in the presence of L-NAME was prevented when indomethacin was given concomitantly. TC treatment increased histamine output in the lumen, a process that was enhanced by L-NAME but reduced by indomethacin. CONCLUSIONS: Damage to the stomach increases both NO and PG in the lumen, and decreases acid secretion. Inhibiting NO production increases acid secretion in the damaged stomach, but only when PG biosynthesis is intact. It is assumed that endogenous PG has a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect probably through enhancing the release of mucosal histamine.

Animals↗
PubMed2000

Prognostic factors in ovarian carcinosarcoma: a clinicopathological and immunohistochemical analysis of 23 cases.

UNLABELLED: Carcinosarcoma of the ovary is a rare, highly aggressive neoplasm comprising histologically of both epithelial and mesenchymal components. The aim of this study was to evaluate the clinicopathological prognostic factors in ovarian carcinosarcoma, including the immunohistochemical expression of p53 protein and Ki67. METHODS AND RESULTS: Twenty-three cases of carcinosarcoma of the ovary were studied retrospectively. The clinicopathological and immunohistochemical parameters including p53 and Ki67 staining were statistically analysed to investigate the prognostic significance of this tumour. The overall 5-year survival rate was 27.1%; 100% for stage I, 31.3% for stage II, 10.9% for stage III and 0% for stage IV. The low-stage group (stages I and II) was found to be a significant prognostic factor for patient survival (P = 0.0113). None of the other factors (tumour size, histological type of carcinomatous and sarcomatous components, mitotic count, vascular space invasion and immunoreactivity for p53 protein and Ki6 7) was found to be a statistically significant prognostic indicator. CONCLUSIONS: Ovarian carcinosarcoma is a rare malignancy with poor prognosis. In this study, advanced stage appears to be poor prognostic indicator of survival in patients with ovarian carcinosarcoma.

Adult↗
PubMed2000

Regulatory mechanism of acid secretion in the damaged stomach: role of endogenous nitric oxide.

The present article overviews the regulatory mechanism of acid secretion in the stomach after damage with taurocholate (TC), one of the bile acids. Mucosal exposure of a rat stomach to 20 mmol/L TC for 30 min caused a decrease of acid secretion with a concomitant increase in nitric oxide (NO) and prostaglandin (PG) E2 (PGE2) as well as Ca2+ in the luminal contents. Prior administration of N(G)-nitro-L-arginine methyl ester (L-NAME), as well as indomethacin, significantly attenuated the reduction of acid secretion by TC and acid secretion was even increased in the presence of L-NAME. The acid stimulatory effect of L-NAME in the damaged stomach was not mimicked by aminoguanidine and was antagonized by co-administration of L-arginine but not D-arginine. Increased NO release in the damaged stomach was suppressed by pretreatment with L-NAME or co-application of EGTA and the latter also inhibited the increase in luminal Ca2+. The enhanced acid secretory response in the presence of L-NAME was also inhibited by cimetidine, FPL-52694 (a mast cell stabilizer) or sensory deafferentation. Mucosal exposure to TC caused an increase in luminal histamine output, together with a decrease in the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 and sensory deafferentation and were also partly suppressed by indomethacin. In addition, the acid stimulatory action of L-NAME in the damaged stomach was significantly mitigated when indomethacin was administered together with L-NAME. We conclude that: (i) damage in the stomach may activate acid a stimulatory pathway in addition to a PG-, NO- and Ca2+-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion; (ii) acid stimulation in the damaged stomach is mediated by histamine released from the mucosal mast cell, a process interacting with capsaicin-sensitive sensory nerves; (iii) the increase in luminal Ca2+ plays a role in increasing NO production and, hence, in regulating acid secretion; and (iv) PG may have a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect, probably through enhancing the release of mucosal histamine.

Animals↗
PubMed2000

Effect of ecabet disodium, a novel locally-acting antiulcer drug, on epithelial restitution following injury by hypertonic NaCl in bullfrog stomach in vitro.

BACKGROUND: The antiulcer drug ecabet 2Na (12-sulfodehydroabietic acid disodium salt) exhibits a gastroprotective activity, mainly through a local action, involving endogenous prostaglandins (PGs) and nitric oxide (NO). In the present study, we examined the effect of ecabet on the epithelial restitution of the bullfrog gastric mucosa in vitro following injury by hypertonic NaCl. METHODS: Bullfrog fundic mucosa was mounted in an Ussing chamber. The tissue injury was induced by exposure of the mucosa to 1.25 M NaCl for 5 min, and transmucosal potential difference (PD) and electrical resistance (R) were measured during a 4-hour test period. Ecabet (3-30 mg/ml) was added to the luminal solution for 10 min before or after NaCl, while 16,16-dimethyl PGE(2) (dmPGE(2): 1x 10(-6) M) or NOR-3 (a NO donor: 1 x 10(-4) M) was added to the nutrient solution 10 min before NaCl. RESULTS: Mucosal application of 1.25 M NaCl caused an immediate reduction of PD and R, followed by a gradual normalization, reaching about 70% of the pre-exposure levels within 4 h. Ecabet, added before NaCl, significantly expedited the recovery of PD and R in a concentration-dependent manner; this effect was mimicked by posttreatment with ecabet and significantly mitigated by prior addition of indomethacin (1 x 10(-5) M) or N(G)-nitro-L-arginine methyl ester (L-NAME: 1 x 10(-3) M). The epithelial restitution was also significantly promoted by serosal application of either dmPGE(2) or NOR-3. The mucosal exposure to ecabet significantly increased the luminal release of PGE(2) and NO metabolites, the effects being attenuated by indomethacin and L-NAME, respectively. The mucous secretion was increased by ecabet as well as dmPGE(2) and NOR-3, and the effect of ecabet was significantly suppressed by both indomethacin and L-NAME. The inhibitory effects of L-NAME on the ecabet action were all significantly antagonized by concurrent addition of L-arginine. CONCLUSION: These results suggest that ecabet significantly expedited the restitution following gastric surface cell injury, and this action is mediated by endogenous NO as well as PGs and may be functionally associated with an increase of mucous secretion.

Abietanes↗
PubMed2000

Relationship between chromosomal instability and intratumoral regional DNA ploidy heterogeneity in primary gastric cancers.

The purpose of this study was to elucidate the relationship between intratumoral regional heterogeneity in DNA ploidy and chromosomal instability (CIN) in primary gastric adenocarcinomas. In 45 sporadic gastric adenocarcinomas, we measured DNA ploidy and numerical aberrations for chromosomes 7, 11, 17, and 18 by laser scanning cytometry and fluorescence in situ hybridization, respectively, in small tissue specimens taken from 2 to 6 (on the average 4) different portions of the same tumor. A total of 231 specimens including 45 normal control specimens were examined. All 98 tumor specimens with DNA aneuploidy (DNA index > or = 1.2) showed large intercellular variations in chromosome copy number, indicating CIN. In contrast, 85 tumor specimens with (near) diploidy (1.0 < or = DNA index < 1.2) exhibited much small intercellular variations in chromosome copy number as compared with aneuploid specimens (P < 0.0001). The relationship between DNA ploidy and intercellular variation in chromosome copy number was true for tumors consisting of a mixture of (near) diploid and aneuploid subpopulations. These data indicate that DNA aneuploidy is associated with CIN but that (near) diploidy is not. Intratumoral regional DNA ploidy heterogeneity was conspicuous in 33 (92%) of 36 tumors with regions of DNA aneuploidy, and all aneuploid specimens showed great intercellular variation in chromosome copy number. Diploid regions were predominant in early stage cancers (intramucosal and submucosal cancers), and five of eight early cancers contained only diploid population. In contrast, all tumors without (near) diploid regions were advanced cancers. These observations suggest that CIN is a necessary prerequisite for developing intratumoral DNA ploidy heterogeneity with DNA aneuploidy.

Adenocarcinoma↗
PubMed1999

Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5.

HIV-2 GH-1 is a molecular clone derived from an AIDS patient from Ghana. In contrast to the prototypic molecular clone ROD, GH-1 exhibits a narrow range of target cell specificity. By an infectious assay using HeLa-CD4 cells stably transfected with an HIV-1 LTR-beta-galactosidase reporter gene and transiently expressing various cloned chemokine receptors, we have examined the coreceptor usage of GH-1. In contrast to ROD, which uses principally CXCR4, GH-1 was found to use mainly if not exclusively CCR5 but not CXCR4. The distinct coreceptor usage of these two molecular clones allowed us to further map the region of gp120 that is important for the coreceptor specificity. By constructing a series of chimeric viruses between GH-1 and ROD, we have demonstrated that the C-terminal half of the V3 loop region of gp120 determines the differential coreceptor usage between GH-1 and ROD, and only a few amino acid differences in this region appear to be able to shift the specificity between CCR5 and CXCR4. Notably, the shift in the coreceptor usage from CCR5 to CXCR4 is associated with an increase in the net positive charge in the V3 region.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Effects of endothelin-1 on duodenal bicarbonate secretion and mucosal integrity in rats.

Effects of endothelin-1 on gastric acid secretion, duodenal HCO3- secretion, and duodenal mucosal integrity were investigated in anesthetized rats, in comparison with those of TY-10957, a stable analogue of prostacyclin. A rat stomach mounted on an ex-vivo chamber or a proximal duodenal loop was perfused with saline, and gastric acid or duodenal HCO3- secretion was measured using a pH-stat method and by adding 100 mM NaOH or 10 mM HCl, respectively. Duodenal lesions were induced by mepirizole (200 mg/kg) given subcutaneously. Intravenous administration of endothelin-1 (0.6 and 1 nmol/kg) caused an increase of duodenal HCO3- secretion with concomitant elevation of blood pressure; this effect was antagonized by co-administrahon of BQ-123 (ET(A) antagonist; 3 mg/kg, i.v.) and significantly mitigated by vagotomy. Likewise, endothelin-1 caused a significant decrease in histamine-stimulated acid secretion, and this effect was also significantly antagonized by BQ-123. Although TY-10957 (10 and 30 mg/kg, i.v.) produced a temporal decrease of blood pressure, this agent caused not only an increase of duodenal HCO3- secretion, independent of vagal nerves, but also a decrease of acid secretion as well. In addition, both endothelin-1 and TY-10957 significantly prevented mepirizole-induced duodenal lesions at the doses that caused an increase of duodenal HCO3- secretion and a decrease of gastric acid secretion. These results suggest that endothelin-1 affects the duodenal mucosal integrity by modifying both gastric acid and duodenal HCO3- secretions, the effects being mediated by ET(A) receptors.

Animals↗