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Biomedical subjects

T D Nguyen

Publications and source records attributed to T D Nguyen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effects of endothelin receptor antagonists and nitric oxide on myogenic tone and alpha-adrenergic-dependent contractions of rabbit resistance arteries.

UNLABELLED: Regulation of vascular contractions by endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) may vary depending on the stimulus. OBJECTIVES: To investigate if ET-1 receptor stimulation and NO contributed to a similar extent to the regulation of pressure- and alpha-adrenergic receptor (AR) agonist-induced smooth muscle contraction. METHODS: Rabbit mesenteric arteries (150-200 microns) were isolated, cannulated and pressurized. Changes in diameter were recorded as a function of the perfusion pressure (PP) or alpha-AR agonist addition at a PP of 60 mmHg. All experiments were performed in the presence of indomethacin (10 mumol 1(-1)). RESULTS: At a PP of 60 mmHg, myogenic tone (MT) developed to represent 17 +/- 1% of the minimal diameter. The magnitude of the MT was increased by 140% (P < 0.05) by the inhibition of NO production with N omega-nitro-L-arginine (L-NOARG). Bosentan, an ETA/B receptor antagonist, and BQ 123, a selective ETA receptor antagonist, decreased (P < 0.05) MT either alone or in combination with L-NOARG by approximately 30%. Phenylephrine (Phe), an alpha 1-AR agonist, induced contraction; the sensitivity to Phe (pD2, 6.2 +/- 0.2) was unaffected by bosentan or BQ 123 alone but increased (P < 0.05) by L-NOARG (pD2, 7.3 +/- 0.5). Further addition of bosentan or BQ 123 restored the sensitivity to Phe to its control value. Oxymetazoline (OXY), an alpha 2-AR agonist, induced contraction; the sensitivity to OXY (pD = 2, 7.7 +/- 0.2) was unaffected by L-NOARG, bosentan or BQ 123. CONCLUSION: Our results indicate that pressure-induced tone is independently regulated by endothelium-derived NO and ET-1. In contrast, alpha 1-AR stimulation-induced tone is sensitive to ET-1 in the absence of NO, whereas occupation of alpha 2-AR mediates a contraction unregulated by the endothelium.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1999

Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer.

Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t(s)= energy (J/cm2) x surface (cm2)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy.

Adult↗
PubMed1999

CYP2E1 and CYP3A1/2 gene expression is not associated with the ursodeoxycholate effect on ethanol-induced lipoperoxidation.

Ethanol is a well-known hepatotoxicant inducing steatosis and membrane lipoperoxidation. The aim of the present study was to investigate in rats, whether the protective effect of UDC on ethanol-induced lipid peroxidation may be related with CYP2E1 and CYP3A1/2 gene expression. We showed that UDC treatment in ethanol-fed rats induced a significant decrease in liver triglyceride concentration which was closely correlated with a reduction in malondialdehyde and hydroxyalkenal levels. In chronically ethanol-fed rats, CYP2E1 and CYP3A1/2 gene expressions were increased by a post-transcriptional mechanism. These inductions, mainly of CYP2E1, could take part in alcohol-induced hepatic lipoperoxidation. UDC modified neither the specific activity, nor the protein level, nor the mRNA level of CYP2E1 when compared with control. UDC supplementation to alcohol diet did not prevent the increase in CYP2E1 expression of ethanol-fed rats. Furthermore, CYP3A1/2 protein levels were similarly increased by ethanol and ethanol plus UDC treatment. Therefore, UDC protective effect against ethanol-induced lipoperoxidation was not associated with a modification of CYP2E1 and CYP3A1/2 expression.

Animals↗
PubMed1999

Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2.

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris.

Animals↗
PubMed1998

GLC1A mutations point to regions of potential functional importance on the TIGR/MYOC protein.

PURPOSE: The aim of this study was to screen affected members of glaucoma families for mutations in the Trabecular Meshwork Inducible Glucocorticoid Response (TIGR) gene also known by the name myocilin (MYOC) or by combined names such as TIGR/MYOC. Our primary objectives were (1) to identify mutations responsible for glaucoma in members of three families for which we have shown linkage between chromosome 1 GLC1A-region markers and the primary open angle glaucoma (POAG) phenotype, and (2) to determine the relationship of these and other mutations to key points of predicted function and structure of the TIGR/MYOC protein. METHODS: DNA sequence determination was used to identify sequence changes in sections of the TIGR/MYOC gene that were PCR-amplified from genomic DNA from the probands of three previously-reported GLC1A juvenile-onset POAG families, UM:JG1, UM:JG3, UM:GL57, and unmapped family UM:JG5. Allele-specific oligonucleotide hybridization was used to screen for the identified mutations in PCR-amplified DNA from individual members of each pedigree and from a panel of 11 additional juvenile glaucoma family probands, 42 adult POAG family probands, and 43 normal individuals. Computerized algorithms were used to identify functional motifs and predict structures of normal and mutant forms of the protein. RESULTS: Sequence changes were found that alter amino acids in the olfactomedin-like domain near the carboxy terminal end of the TIGR protein in affected members of families UM:JG1 (Pro370Leu), UM:JG3 (Val426Phe), UM:GL57 (Glu323Lys) and UM:JG5 (Gly252Arg). Co-segregation of glaucoma and Pro370Leu, Val426Phe, and Gly252Arg in known GLC1A families suggests that these are mutations. Although the Gly252Arg substitution observed in UM:JG5 is non-conservative, it was not possible to distinguish whether it is a mutation or a polymorphism. None of the sequence changes described in these families were observed in other juvenile glaucoma cases in this study, nor in any of the POAG or phenotypically normal individuals tested here. Analysis of amino acid sequence changes resulting from mutations described in this and other works demonstrate localization of many mutations in the vicinity of predicted functional motifs in the olfactomedin-like domain. Identification of rat latrophilin (LPH1/CIRL) as a new member of the olfactomedin-like protein family to which TIGR/MYOC belongs suggests that the region of olfactomedin homology is a protein domain that can occur in different protein contexts. CONCLUSIONS: Location of mutations described in this and previous work suggests that some specific predicted protein motifs in the olfactomedin-like domain may be important to TIGR/MYOC function. In some cases, the role of TIGR/MYOC in the etiology of glaucoma may result from alteration of the sequences recognized by modifying enzymes such as casein kinase II. In other cases altered protein folding may affect access of enzymes to their target sequences on TIGR/MYOC. Although modifications and structures discussed here are predicted rather than proven, they provide a useful theoretical framework for design of subsequent experiments. Alterations to protein folding and predicted modification motifs cannot explain the pathogenic mechanisms of all of the known TIGR/MYOC glaucoma mutations.

Adult↗
PubMed1998

A review of the present status of lymphatic filariasis in Vietnam.

Establishing the current status of an infectious disease forms the starting point of any attempt at parasite control. Although data on the prevalence and distribution of lymphatic filariasis exist for Vietnam from the early 1900s, the present situation regarding the disease is less well-known. Here, we review the results of recent surveys conducted by the Institute of Malariology, Parasitology and Entomology, Hanoi, to update the existing information on filariasis epidemiology and distribution for this country. The present results are from surveys carried out on some 135,000 individuals in 24 provinces of Vietnam. The highest prevalences of microfilaraemia (primarily Brugia malayi ) are observed in lowland areas of the Red River Delta and in Quang-binh Province where the survey results show microfilaraemia (mf) prevalences in the range of 0.9-5.5%. The most common type of chronic clinical manifestation is shown to be leg elephantiasis. A significant finding is that an overall decrease in mf prevalence was observed to occur in five communities which were surveyed twice over an 11-21-year period, even though no interventions were carried out between the two surveys. The changes are probably caused by environmental changes, such as increased standards of housing and drainage. Studies on the effect of selective chemotherapy and mass chemotherapy using diethylcarbamazine showed reductions in community mf prevalences of 69 and 72-88%, respectively. Furthermore, cats do not appear to represent significant reservoirs of infection. These findings of geographical restriction of infection, effective and well-tolerated drug therapy, low significance of animal reservoirs, together with the existence of an effective national health network, suggest a good prognosis for the control of filariasis in this country.

Animals↗
PubMed1998

Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells.

Expression of the trabecular meshwork inducible glucocorticoid response (TIGR) gene progressively increases from barely detectable levels to greater than 2% of total cellular mRNA over 10 days exposure of trabecular meshwork (TM) cells to dexamethasone. Cycloheximide blocked most of the TIGR mRNA induction, suggesting a requirement for ongoing protein synthesis. The genomic structure of TIGR (approximately 20 kilobases) consists of 3 exons, and a 5-kilobase promoter region that contains 13 predicted hormone response elements, including several glucocorticoid regulatory elements, and other potentially important regulatory motifs. TIGR cDNA encodes an olfactomedin-related glycoprotein of 504 amino acids with motifs for N- and O-linked glycosylation, glycosaminoglycan initiation, hyaluronic acid binding, and leucine zippers. Recombinant TIGR (rTIGR) showed oligomerization and specific binding to TM cells. Anti-rTIGR antibody detected multiple translational/post-translational forms of TIGR produced by the cells (including secreted 66 kDa/55 kDa glycoproteins/proteins in the media and 55 kDa cellular proteins), whereas Northern blot showed a single mRNA species. The findings suggest potential mechanisms by which TIGR could obstruct the aqueous humor fluid flow and participate in the pathogenesis of glaucoma.

Amino Acid Sequence↗
PubMed1998

Molecular structure and expression of shaker type potassium channels in glial cells of trout CNS.

Two shaker-related potassium channel transcripts (tsha1, tsha2) were identified in glial cells of trout central nervous system (CNS) by polymerase chain reaction (PCR)-cloning and sequencing. While tsha1 was highly similar to the mammalian Kv1.2 subtype of potassium channels, tsha2 did not show a preferential sequence homology with a particular subtype of shaker, but exhibited uniform similarity with mammalian Kv1.1, Kv1.2, and Kv1.3, respectively. Transcripts for the shaw and shal subfamilies of voltage-gated potassium channels were detected in whole brain tissue only but not in freshly dissociated glial cells. Using mRNA extracted from different glial cell types in combination with sequence specific PCR primers, tshal was found restricted to oligodendrocytes and their progenitor cells, while tsha2 was common to astrocytes, as well.

Amino Acid Sequence↗
PubMed1998

Characteristics of patients less than 45 years of age compared with older patients undergoing coronary artery bypass grafting.

BACKGROUND: Coronary artery disease (CAD) was not recognized as common among young patients until the study by Yater in 1948. Subsequent studies further elucidated the nature of the disease, which had become more apparent in the younger groups. HYPOTHESIS: The study was undertaken to determine the prevalence of risk factors and severity of coronary disease among young patients aged < or = 45 years undergoing coronary artery bypass grafting (CABG) compared with older patients. METHODS: In all, 112 young patients aged < or = 45 years (Group 1) and 798 older patients aged > 45 years (Group 2) were analyzed for trends to hypertension, smoking, diabetes, family history of heart disease, hypercholesterolemia, obesity, and history of previous myocardial infarction (MI). The severity of disease was examined in terms of number of diseased vessels, vessel size, number of grafts performed, performance of endarterectomies, and left ventricular function. RESULTS: Group 1 had a higher incidence of positive family history (68.5 vs. 51.2%, p < 0.05), and lower incidences of hypertension (62.7 vs. 81.5%, p < 0.05), obesity (42.9 vs. 83.9%, p < 0.05), and history of previous MI (54.5 vs. 94.6%, p < 0.05). Group 2 had a higher incidence of left main disease (22.6 vs. 11.4%, p < 0.05). The distribution of the affected vessels of the young patients was most commonly the left anterior descending (90.4%) followed by the right coronary (79.8%) and circumflex arteries (69.2%). Group 2 had more grafts per patient (3.82 vs. 3.37, p < 0.05). The size of the diseased vessels measured intraoperatively was similar (1.56 vs. 1.58 mm, p = NS) in both groups. Endarterectomy was performed almost three times more often in Group 1 patients (8.2 vs. 3.0%, p < 0.05). Operative mortality was less in Group 1 mean (1.8 vs. 6.3%, p < 0.05). Group 2 had a greater mean left ventricular ejection fraction (53.8 vs. 49.7%, p < 0.05). CONCLUSION: Compared with the older population, patients < or = 45 years of age who underwent CABG had (1) a higher incidence of positive family history of CAD, (2) a higher likelihood of requiring an endarterectomy, and (3) lower operative mortality rate despite a slightly poorer ventricular function.

Adult↗
PubMed1998

Culture of human main pancreatic duct epithelial cells.

Attempts to grow human pancreatic duct epithelial cells in long-term culture have proven difficult. We have developed a system of growing these cells for several passages by adapting methods used to culture dog pancreatic duct cells. Epithelial cells were enzymatically dissociated from the main pancreatic duct and plated onto collagen-coated culture inserts suspended above a human fibroblast feeder layer. After primary culture, the cells were either passaged onto new inserts or plastic tissue culture plates in the absence of collagen. Cells grown on the latter plates were maintained in a serum-free medium. Primary pancreatic duct epithelial cells grow steadily to confluence as a monolayer in the feeder layer system. After primary culture, cells passaged onto new inserts with fresh feeder layer or plastic plates and fed with serum-free medium continued to develop into confluent monolayers for up to four passages. The cells were columnar with prominent apical microvilli, sub-apical secretory vesicles, and lateral intercellular junctions resembling the morphology of normal in vivo epithelial cells. These cells were also positive for cytokeratin 19, 7, and 8 and carbonic anhydrase II, as measured by immunohistochemistry. Metabolically, these cells synthesized and secreted mucin, as measured by incorporation of tritiated N-acetyl-D-glucosamine. In conclusion, we demonstrated that human pancreatic epithelial cells from the main duct can be successfully grown in culture and repeatedly passaged using a feeder layer system, with serum-free medium, and in organotypic cultures.

Cell Culture Techniques↗
PubMed1998

Effect of mast cell granules on the gene expression of nitric oxide synthase and tumour necrosis factor-alpha in macrophages.

Previous studies have shown that mast cell granules (MCG) inhibit numerous macrophage functions including tumour cytotoxicity, superoxide and nitric oxide (NO) production, and FCgamma2a receptor-mediated phagocytosis. In this study, the effect of MCG on macrophage TNF alpha and nitric oxide synthase (iNOS) mRNA expression, and the production and fate of TNF alpha were examined. Upon activation with LPS+IFN gamma, macrophages expressed both TNF alpha and iNOS mRNA and produced both TNF alpha and NO. Co-incubation of LPS+IFN gamma-activated macrophages with MCG resulted in dose-dependent inhibition of iNOS mRNA expression. TNF alpha production in the activated macrophages was decreased by MCG, which was associated with a reduction in TNF alpha mRNA expression. MCG were also capable of degrading both macrophage-generated and recombinant TNF alpha. The direct effect of MCG on TNF alpha was partially reversed by a mixture of protease inhibitors. These results demonstrate that MCG decrease the production of NO and TNF alpha by inhibiting macrophage iNOS and TNF alpha gene expression. Furthermore, MCG post-transcriptionally alter TNF alpha levels via proteolytic degradation.

Animals↗
PubMed1998

Calcium-activated potassium conductances on cultured nontransformed dog pancreatic duct epithelial cells.

Pancreatic duct epithelial cells (PDECs) mediate the pancreatic secretion of fluid and electrolytes. Membrane K+ channels on these cells regulate intracellular K+ concentration; in combination with the Na+/H+ antiport and Na+,K+ adenosine triphosphatase (ATPase), they may also mediate serosal H+ secretion, balancing luminal HCO3- secretion. We describe the K+ conductances on well-differentiated and functional nontransformed cultured dog PDECs. Through 86Rb+ efflux studies, we demonstrated Ca(2+)-activated K+ channels that were stimulated by A23187, thapsigargin, and 1-ethyl-2-benzimidazolinone, but not forskolin. These conductances also were localized on the basolateral membrane because 86Rb+ efflux was directed toward the serosal compartment. Of the K+ channel blockers, BaCl2, charybdotoxin, clotrimazole, and quinidine, but not 4-aminopyridine, apamin, tetraethylammonium, or iberiotoxin, inhibited 86Rb+ efflux. This efflux was not inhibited by amiloride, ouabain, and bumetanide, inhibitors of the Na+/H+ antiport, the Na+,K(+)-ATPase pump, and the Na+,K+,2Cl- cotransporter, respectively. When apically permeabilized PDEC monolayers were mounted in Ussing chambers with a luminal-to-serosal K+ gradient, A23187 and 1-ethyl-2-benzimidazolinone stimulated a charybdotoxin-sensitive short-circuit current (Isc) increase. Characterization of K+ channels on these cultured PDECs, along with previous identification of Cl- channels (1), further supports the importance of these cells as models for pancreatic duct secretion.

Animals↗
PubMed1998

The TIGR gene, pathogenic mechanisms, and other recent advances in glaucoma genetics.

Important advances have been made within the past year in the area of glaucoma genetics, including the identification of the TIGR gene for adult as well as juvenile GLC1A glaucoma, a P450 gene for GLC3A congenital glaucoma, and a bicoidhomeobox transcription factor gene RIEG for developmental glaucoma. The cloning of TIGR as a candidate gene for glaucoma is based on its distinctive induction in human trabecular meshwork cells and tissues, its induction profile, and the expressed molecule's putative biologic properties. Results from several laboratories showing defects in the olfactomedin homology domain of the TIGR gene have generated particular interest concerning potential pathogenic mechanisms. Recent progress in glaucoma genetics has also included the identification of new loci in familial adult open-angle glaucoma, the identification of a locus associated with pigment dispersion syndrome, and the collection of new families for linkage analyses and clinical assessments. Taken together, these findings offer future prospects for improving diagnostic criteria, for understanding disease etiologies, and for developing improved therapeutic strategies.

Adolescent↗
PubMed1998

Acute and chronic phases of Toxoplasma gondii infection in mice modulate the host immune responses.

Murine antibody responses to soluble proteins are generally restricted to the immunoglobulin G1 (IgG1) isotype. When mice were infected with Toxoplasma gondii Beverley and concomitantly immunized with a soluble unrelated protein antigen, a modification in the isotypic distribution of antibodies directed against this nonparasite antigen was observed, with a preferential production of IgG2a. Interestingly, when mice were immunized with a soluble protein antigen during the chronic phase (day 40) of infection with T. gondii Beverley, a similar modification in the isotypic distribution of antiprotein antibodies was observed.

Acute Disease↗
PubMed1998

Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells.

Extracellular triphosphate nucleotides, such as ATP, may regulate various cellular functions through specific cell surface receptors. We examine in this report the different secretory effects of ATP and analogs on nontransformed dog pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine 5'-O-(3-thiotriphosphate), and, to a lesser extent, beta, gamma-methylene-ATP, but not adenosine, stimulated 125I- efflux from PDEC, suggesting a primary role for P2Y2 receptors, 2) ATP-stimulated 125I- efflux was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting mediation through Ca2+-activated Cl- channels, 3) ATP stimulated an 86Rb+ efflux sensitive to BaCl2 and charybdotoxin, thus likely occurring through Ca2+-activated K+ channels, 4) serosal or luminal addition of UTP activated apical Cl- conductance and basolateral K+ conductance when nystatin-permeabilized PDEC were studied in an Ussing chamber, suggesting the expression of P2Y2 receptors on both sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases intracellular Ca2+ concentration ([Ca2+]i). In conclusion, ATP and UTP interact with P2Y2 receptors on nontransformed PDEC to increase [Ca2+]i, stimulate mucin secretion, and activate ion conductances; these findings have implications for pancreatic exocrine function in both health and disease, such as cystic fibrosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Histamine stimulates ion transport by dog pancreatic duct epithelial cells through H1 receptors.

Histamine affects pancreatic secretion, but its direct action on ion transport by pancreatic duct epithelial cells (PDEC) has not been defined. We now characterize the secretory effects of histamine on cultured, well-differentiated, and nontransformed dog PDEC. Histamine stimulated, in a concentration-dependent manner (1-100 microM), a cellular 125I- efflux that was inhibited by 500 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid, 2.5 mM diphenylamine-2-carboxylate, and 500 microM DIDS and thus mediated through Ca2+-activated Cl- channels. Histamine-stimulated 125I- efflux was 1) inhibited by 100 microM diphenhydramine, an H1 receptor antagonist, 2) resistant to 1 mM cimetidine, an H2 receptor antagonist, 3) not reproduced by 1 mM dimaprit, an H2 agonist, and 4) inhibited by 50 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a Ca2+ chelator, suggesting that it was mediated through H1 receptors acting via increased cytosolic Ca2+. Histamine also stimulated a 86Rb+ efflux that was sensitive to 100 nM charybdotoxin and thus mediated through Ca2+-activated K+ channels. When PDEC monolayers were studied in Ussing chambers, a short-circuit current of 21.7 +/- 3.1 microA/cm2 was stimulated by 100 microM histamine. This effect was inhibited by diphenhydramine but not cimetidine, was not reproduced with dimaprit, and was observed only after serosal addition of histamine, suggesting that it was mediated by basolateral H1 receptors on PDEC. In conclusion, histamine, acting through basolateral H1 receptors, activates both Ca2+-activated Cl- and K+ channels; in this manner, it may regulate PDEC secretion in normal or inflamed pancreas.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Control of vascular tone by endogenous endothelin-1 in human pial arteries.

BACKGROUND AND PURPOSE: Endothelin-1 (ET) has been shown to be involved in human pathological conditions, but its physiological function remains to be elucidated. The aim of this work was to assess whether endothelium-derived ET was involved in the overall responsiveness of freshly isolated human pial arteries. METHODS: Samples of cerebral cortex, otherwise discarded, were obtained during tumor or epileptic lesion resections (n = 10 donors). Arterial segments were isolated and mounted on a microvessel myograph. RESULTS: Inhibition of nitric oxide (NO) formation with N omega-nitro-L-arginine (L-NA, 100 micromol/L) increased basal tone by 7+/-1% Emax (n=5). This increase in tone was fully abolished in the presence of BQ123 (1 micromol/L; ET(A) receptor antagonist, P<.05) but potentiated by a subthreshold concentration of exogenous ET (1 nmol/L; 33+/-8% Emax; P<.05). In the presence of L-NA, serotonin (10 micromol/L)-induced tone was doubled compared with the control response (P<.05) but reduced by 90% in the presence of BQ123 (P<.05). In the absence of L-NA, BQ123 prevented serotonin-induced tone (n=3). Oxymetazoline, a selective alpha2-adrenergic receptor agonist, induced an endothelium-dependent relaxation of preconstricted human pial arteries. The relaxation was partially sensitive to NO synthase inhibition and fully prevented by the addition of ET, whereas substance P-induced relaxation was preserved. Glibenclamide (1 micromol/L), an inhibitor of ATP-sensitive K+ channels and tetraethylammonium (1 mmol/L), an inhibitor of Ca2+-activated K+ channels had no effect on oxymetazoline-induced relaxation. CONCLUSIONS: The results of this study suggest first that ET is involved in the tonic response induced by NO synthase inhibition; second, part of the contractile response induced by serotonin is endothelium-dependent and sensitive to BQ123; and third, the data suggest that activation of alpha2-adrenergic receptors generated an endothelium-dependent relaxation that was selectively inhibited by exogenous ET.

Adolescent↗