Biomedical subjects

K Iinuma

Publications and source records attributed to K Iinuma.

At least 37 records · Page 2Linked to original sources

PubMed2001

"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.

BACKGROUND: While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. To elucidate the basis for this paradoxical immaturity in urine-concentrating ability, we investigated the function of Henle's loop and collecting ducts (IMCDs) in the inner medulla of neonatal rat kidneys. METHODS: Analyses of individual renal tubules in the inner medulla of neonatal and adult rat kidneys were performed by measuring mRNA expression of membrane transporters, transepithelial voltages, and isotopic water and ion fluxes. Immunofluorescent identification of the rCCC2 and rCLC-K1 using polyclonal antibodies was also performed in neonatal and adult kidney slices. RESULTS: On day 1, the transepithelial voltages (V(Ts)) in the thin ascending limbs (tALs) and IMCDs were 14.6 +/- 1.1 mV (N = 27) and -42.7 +/- 6.1 mV (N = 14), respectively. The V(Ts) in the thin descending limbs (tDLs) were zero on day 1. The V(Ts) in the tALs were strongly inhibited by luminal bumetanide or basolateral ouabain, suggesting the presence of a NaCl reabsorption mechanism similar to that in the thick ascending limb (TAL). The diffusional voltage (V(D)) of the tAL due to transepithelial NaCl gradient was almost insensitive to a chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The V(Ts) in the IMCDs were strongly inhibited by luminal amiloride. On day 1, both the tDL and tAL were impermeable to water, indicating the water impermeability of the entire loop. Diffusional water permeability (P(dw)) and urea permeabilities (P(urea)) in the IMCDs indicated virtual impermeability to water and urea on day 1. Stimulation by vasopressin (1 nmol/L) revealed that only P(dw) was sensitive to vasopressin by day 14. A partial isoosmolar replacement of luminal urea by NaCl evoked negligible water flux across the neonatal IMCDs, indicating the absence of urea-dependent volume flux in the neonatal IMCD. These transport characteristics in each neonatal tubule are similar to those in quail kidneys. Identification of mRNAs and immunofluorescent studies for specific transporters, including rAQP-1, rCCC2, rCLC-K1, rENaC beta subunit, rAQP-2, and rUT-A1, supported these findings. CONCLUSION: We hypothesize that the renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla. The qualitative changes in the organization of medullary tubules may be primarily responsible for the immature urine-concentrating ability in mammalian neonates.

Age Factors↗

PubMed2001

LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.

BACKGROUND & AIMS: One approach to the development of targeted cancer chemotherapy exploits increased uptake of the agent into neoplastic cells. In this scenario, higher concentrations of the agent in cancer cells are responsible for differential killing, whereas the low concentration in normal human cells decreases side effects. The aim of this study was to isolate an organic anion transporter that is weak in normal cells, but abundantly expressed in cancer cells, to deliver the anticancer drugs to the cells. METHODS: A human liver complementary DNA (cDNA) library was screened with liver-specific transporter (LST)-1 cDNA as a probe. Northern blot analyses were performed using the isolated cDNA (termed LST-2). An LST-2-specific antibody was raised, and immunohistochemical analyses including immunoelectron microscopy were performed. Xenopus oocyte expression system was used for functional analysis. We also established a permanent cell line that consistently expresses LST-2 to examine the relationship between methotrexate uptake and sensitivity. RESULTS: The isolated cDNA, LST-2, has 79.7% of overall homology with human LST-1. LST-2 exclusively expressed in the liver under normal conditions and its immunoreactivity was highest at the basolateral membrane of the hepatocytes around the central vein. Although its weak expression in the liver, LST-2 is abundantly expressed in the gastric, colon, and pancreatic cancers. On the other hand, the LST-1 was only detected in a hepatic cell line. LST-2 transports methotrexate in a saturable and dose-dependent manner. Furthermore, introduction of the LST-2 gene into mammalian cells potentiates sensitivity to methotrexate. CONCLUSIONS: LST-2 is one of the prime candidate molecules for determining methotrexate sensitivity and may be a good target to deliver anticancer drugs to the gastrointestinal cancers.

Amino Acid Sequence↗

PubMed2001

Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner.

We have recently identified that rat organic anion transporters, polypeptide2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has diverged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identified by us. In this study we isolated and characterized a novel human organic anion transporter, OATP-E from human brain. The isolated complementary DNA encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the phylogenetic tree analysis revealed that OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E transported 3,3',5-triiodo-L-thyronine (K(m), 0.9 microM), thyronine, and rT(3) in a Na(+)-independent manner. Although the clone was isolated from the brain, OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The rat counterpart, oatp-E, also transported 3,3',5-triiodo-L-thyronine. In addition, in this study we revealed that human OATP, which is exclusively expressed in the brain, transported 3,3',5-triiodo-L-thyronine (K(m), 6.5 microM), T(4) (K(m), 8.0 microM), and rT(3). These data suggest that in humans, several different molecules are involved in transporting thyroid hormone: OATP in the brain, LST-1 in the liver, and OATP-E in peripheral tissues.

Amino Acid Sequence↗

PubMed2001

Urine-based enzyme-linked immunosorbent assay for the detection of Helicobacter pylori infection in children.

OBJECTIVE: Serology and (13)C-urea breath test have been widely used as noninvasive tests to detect Helicobacter pylori infection. However, easier collection of samples and lower costs are desirable for diagnosis of the individual patient or for use in epidemiologic studies. Our aim was to study the diagnostic accuracy of a recently developed urine-based enzyme-linked immunosorbent assay (ELISA) kit for the detection of H pylori-specific immunoglobulin G (IgG) antibodies in children. STUDY DESIGN: Specimens of serum and randomly voided urine were collected from 816 children (0-15 years old) and were analyzed using 2 serum-based ELISA kits and a urine-based ELISA kit, respectively. Based on results of serology, the sensitivity, specificity, and accuracy of the urine-based ELISA kit were evaluated. With regard to false-positive and false-negative results, urinary IgG concentrations and IgG/creatinine levels were studied. RESULTS: Both serum-based ELISAs were positive in 41 children and were negative in 666, who were enrolled in this study. The remaining 109 children were excluded because of disagreement between the results of the 2 serum-based ELISAs, including indeterminate values. Overall sensitivity, specificity, and accuracy of urine-based ELISA test compared with serology were 85.4%, 95.5%, and 94.9%, respectively. On positivity rates, the urine-based ELISA was closely coincident with the serum-based ELISA in each age group. There was no correlation between antibody levels detected by urine-based ELISA and each serum-based ELISA. Urinary IgG concentrations and IgG/creatinine levels were significantly higher in false-positives and were lower in false-negatives than in true-positives plus true-negatives for serology. Most of those with false-positive results had trace to moderate proteinuria. CONCLUSIONS: The urine-based ELISA is an alternative to serum-based ELISA for diagnosis of H pylori infection in children and should be suitable for large-scale epidemiologic studies concerning the organism. In children with proteinuria, results of the test should be interpreted with caution. It is possible that the urine-based ELISA method would be applicable to diagnosis of other infectious diseases.

Adolescent↗

PubMed2001

Monitoring of minimal residual disease in children with acute promyelocytic leukemia by RT-PCR detecting PML/RARalpha chimeric gene: a retrospective study of clinical feasibility.

We studied retrospectively the clinical feasibility of minimal residual disease (MRD) monitoring by reverse transcription-polymerase chain reaction (RT-PCR) detecting the PML/retinoic acid receptor alpha (RARalpha) chimeric gene in children with acute promyelocytic leukemia (APL). MRD monitoring of APL was performed with standard and nested RT-PCR for PML/RARalpha gene, the sensitivity of which was 1 leukemic cell in 10(3)-10(4) and 1 in 10(4)-10(5) cells, respectively. Patients were nine children with APL (average age: 8.3 year; average period of follow-up: 69.2 months) who, after achieving remission with all-trans retinoic acid (ATRA), received treatment either with multidrug chemotherapy or with a combination of chemotherapy and ATRA. Out of six patients treated with multidrug-combined chemotherapy, two patients exhibited PCR positivity after six months of post- remission therapy, which shifted from the detectable range of the nested PCR to that of the standard PCR. These two patients subsequently relapsed and, together with two of the other patients receiving multidrug-combined chemotherapy, underwent allogeneic bone marrow transplantation. No MRD was detected in these patients after transplantation. In the remaining three patients who underwent cyclic treatment with alternative chemotherapy and ATRA, two showed positive RT-PCR at the nested or standard level, respectively, after six months of combined therapy, and one of them relapsed. Overall, three of four patients with MRD detected in post-remission period ultimately relapsed, while all of five patients without detectable MRD had a good prognosis. These findings suggest that impending relapse may be predicted by the detection of preceding PCR positivity with an increasing quantity of the PML/RARalpha mRNA that appears beyond six months of post-remission chemotherapy, with or without combined ATRA therapy.

Adolescent↗

PubMed2001

Improved survival of children with advanced neuroblastoma treated by intensified therapy including myeloablative chemotherapy with stem cell transplantation: a retrospective analysis from the Tohoku Neuroblastoma Study Group.

In the hospitals of the Tohoku Neuroblastoma Study Group (TNBSG), treatment for children with advanced neuroblastoma (NB) was intensified in the mid-1990's with the introduction of myeloablative therapy (MT) with stem cell transplantation (SCT) including the use of autologous peripheral blood stem cells (PBSC) and bone marrow transplantation (BMT). In this report, we examined whether the intensified therapy improved the outcome of children with advanced NB (age> 12 months) who were diagnosed between 1991 and 1997. Patients were 36 children (23 boys and 13 girls) with an average age of 3.4 years (range; 1 to 14 years). Six of them had stage III disease, and the other 30 had stage IV. They were treated initially with induction chemotherapy, surgery, and post-operative chemoradiotherapy, after which 17 of them continued further chemotherapy and the other 19 received MT/SCT (18 with PBSCT and 1 with BMT). Progression-free survival (PFS) rate at seven years from diagnosis was 43.5% for all patients, 66.7% for stage III patients and 38.2% for stage IV patients. The difference between stage III and IV patients was not significant. Among the 30 patients with stage IV disease, PFS at seven years was significantly higher in the 19 patients who received MT/SCT (55.6%) than in the 11 patients who did not receive it (12.5%). There was no difference in clinical and biological risk factors between these two groups, except for the proportion of patients with favorable response to initial therapy (36% and 80% for patients without and with MT/SCT, respectively). Furthermore, the proportion of patients with N-myc amplification was significantly higher in patients with progressive disease (PD) after MT/SCT than in those in CR after MT/SCT. The results of this retrospective study of children with advanced NB suggest that therapy intensification involving MT/SCT might result in lengthened survival time for patients with stage IV disease, and that post-transplant PD remains a risk for patients with high levels of N-myc amplification.

Antineoplastic Agents↗

PubMed2001

Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival.

Although mesangial cell death has been shown to be correlated with mesangial cell mitosis in vivo, little is known about how these two apparently opposite events are regulated. We show that the addition of platelet-derived growth factor (PDGF; 10-50 ng/ml) to primary cultured rat mesangial cells for 24 h caused continuous proliferation along with simultaneous cell death. This process was accompanied by the fragmentation of DNA into nucleosomal oligomers, the development of apoptotic morphological changes in the nucleus, and increased expression of p53. Accumulation of lactate dehydrogenase (LDH) was also observed in the culture medium, suggesting that both apoptosis and necrosis are involved in the cell death mechanisms observed. We also observed that addition of 30 microM lysophosphatidic acid (LPA) to the culture medium greatly suppressed PDGF-induced cell death, leading to synergistically enhanced mesangial cell proliferation. DNA fragmentation, p53 expression and LDH release were all suppressed by LPA. We suggest that PDGF is a bifunctional molecule in mesangial cells that evokes both cell proliferation and cell death simultaneously, whereas LPA is a survival factor. We speculate that PDGF and LPA may play important roles in the progression or exacerbation of proliferative glomerulonephritis.

Analysis of Variance↗

PubMed2000

Elevated plasma levels of transforming growth factor beta1 in patients with muscular dystrophy.

The progression of muscular weakness of patients suffering from muscular dystrophies directly correlates with the progressive loss of myofibers, accompanied by fibrosis. Since transforming growth factor beta1 (TGF-beta1) promotes tissue fibrosis, we measured the plasma TGF-beta1 level in patients with various muscular dystrophies in order to determine whether the level is elevated in patients with muscular dystrophy and if the level reflects the severity of tissue fibrosis. The plasma TGF-beta1 level was significantly elevated in patients with Duchenne muscular dystrophy and congenital muscular dystrophy (CMD), but not in those with Becker muscular dystrophy. Growth factors related to muscle fiber regeneration and fibrosis might be a key factor in the progression of muscular dystrophy and could be a target for therapeutic studies.

Adolescent↗

PubMed2000

Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate.

We have isolated a rat novel multispecific organic anion transporter, moat1. The isolated clones were originated by alternative splicing of the moat1 mRNA. The nucleotide sequences predict a protein of 682 amino acids with moderate sequence similarity to LST-1, the oatp family, and the prostaglandin transporter. Northern blot analysis of rat moat1 identified a predominant transcript of 4.4 kilonucleotides in all tissues. Northern blot and in situ hybridization analyses of rat brain further indicated that moat1 mRNA is widely distributed in neuronal cells of the central nervous system, especially in the hippocampus and cerebellum. moat1 transports prostaglandin D(2) (K(m); 35.5 nM), leukotriene C(4) (K(m); 3.2 microM) and taurocholate (K(m); 17.6 microM) in a sodium-independent manner. moat1 also transports prostaglandin E(1), E(2), thromboxane B(2), and iloprost but not dehydroepiandrosterone sulfate and digoxin, of which the substrate specificity is similar, but definitively different from those of any other organic anion transporters.

Alternative Splicing↗

PubMed2000

Biosynthesis of PF1022A and related cyclooctadepsipeptides.

PF1022A belongs to a recently identified class of N-methylated cyclooctadepsipeptides (CODPs) with strong anthelmintic properties. Described here is the cell-free synthesis of this CODP and related structures, as well as the purification and enzymatic characterization of the responsible synthetase. For PF1022A synthesis extracts of Mycelia sterilia were incubated with the precursors L-leucine, D-lactate, D-phenyllactate, and S-adenosyl-L-methionine in the presence of ATP and MgCl(2). A 350-kDa depsipeptide synthetase, PFSYN, responsible for PF1022A synthesis was purified to electrophoretic homogeneity. Like other peptide synthetases, PFSYN follows a thiotemplate mechanism in which the substrates are activated as thioesters via adenylation. N-Methylation of the substrate L-leucine takes place after covalent binding prior to peptide bond formation. The enzyme is capable of synthesizing all known natural cyclooctadepsipeptides of the PF1022 type (A, B, C, and D) differing in the content of D-lactate and D-phenyllactate. In addition to PF1022 types A, B, C, and D, the in vitro incubations produced PF1022F (a CODP consisting of D-lactate and N-methyl-L-leucine), as well as di-, tetra-, and hexa-PF1022 homologs. PFSYN strongly resembles the well documented enniatin synthetase in size and mechanism. Our results suggest that PFSYN, like enniatin synthetase, is an enzyme with two peptide synthetase domains and forms CODP by repeated condensation of dipeptidol building blocks. Due to the low specificity of the d-hydroxy acid binding site, D-lactate or D-phenyllactate can be incorporated into the dipeptidols depending on the concentration of these substrates in the reaction mixture.

Adenosine Triphosphate↗

PubMed2000

Glycogen storage disease type Ia: molecular diagnosis of 51 Japanese patients and characterization of splicing mutations by analysis of ectopically transcribed mRNA from lymphoblastoid cells.

Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of glucose-6-phosphatase (G6Pase) that is expressed in the liver, kidney, and intestinal mucosa. Clinical manifestations include short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. To elucidate a spectrum of the G6Pase gene mutations and their frequencies, we analyzed mutations in 51 unrelated Japanese patients with GSD-Ia. The most prevalent mutation was g727t, accounting for 88 of 102 mutant alleles examined, followed by R170X mutation, which accounted for 6 mutant alleles, and R83H mutation which was observed in 3 mutant alleles. In addition, 3 different, novel mutations, IVS1-1g<a, Gly122-to-Asp (G122D) and His179-to-Pro (H179P), were identified. We were able to detect "ectopically" transcribed G6Pase-mRNA in Epstein-Barr virus-transformed lymphoblastoid cells and observed aberrant mRNA splicing associated with the g727t and IVS1-1g<a mutations. To our knowledge, this is the first report that ectopic expression can be utilized for the characterization of GSD-Ia mutations. Our findings suggest that a screening for the g727t, R170X, and R83H mutations by simple DNA-based diagnostic methods can detect 95% of the G6Pase mutant alleles in Japanese patients with GSD-Ia, and remaining mutations can be identified and characterized by the direct sequencing of genomic DNA and/or the analysis of ectopically expressed mRNA. The noninvasive molecular diagnosis for GSD-Ia may ultimately replace the conventional means of enzymatic diagnosis that requires liver biopsy.

Alleles↗

PubMed2000

Mutation detection by TaqMan-allele specific amplification: application to molecular diagnosis of glycogen storage disease type Ia and medium-chain acyl-CoA dehydrogenase deficiency.

We have devised an allele-specific amplification method with a TaqMan fluorogenic probe (TaqMan-ASA) for the detection of point mutations. Pairwise PCR amplification using two sets of allele-specific primers in the presence of a TaqMan probe was monitored in real time with a fluorescence detector. Difference in amplification efficiency between the two PCR reactions was determined by "threshold" cycles to differentiate mutant and normal alleles without post-PCR processing. The method measured the efficiency of amplification rather than the presence or absence of end-point PCR products, therefore allowing greater flexibility in designing allele-specific primers and an ample technical margin for allelic discrimination. We applied the TaqMan-ASA method to detect a prevalent 727G>T mutation in Japanese patients with glycogen storage disease type Ia and a common 985A>G mutation in Caucasian patients with medium-chain acyl-CoA dehydrogenase deficiency. The method can be automated and may be applicable to the DNA diagnosis of various genetic diseases.

Acyl-CoA Dehydrogenase↗

PubMed2000

Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy.

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.

Amantadine↗

PubMed2000

The perfusion defect seen with SPECT in West syndrome is not correlated with seizure prognosis or developmental outcome.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

Cerebral Cortex↗

PubMed2000

CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease.

cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.

Adolescent↗

PubMed2000

Mutation analysis of the GLUT2 gene in patients with Fanconi-Bickel syndrome.

Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder manifesting hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Several mutations in a gene encoding a glucose transporter, GLUT2, have recently been reported in patients with FBS. We performed molecular analysis on three Japanese patients and found four novel mutations: a splice-site mutation (IVS2-2A>G), a nonsense mutation (Q287X), and two missense mutations (L389P and V423E). Heterozygotes of L389P or V423E mutation from the patients' families showed renal glucosuria. These data suggested that GLUT2 gene defects may be a cause of renal glucosuria.

Adolescent↗

PubMed2000

17beta-hydroxysteroid dehydrogenase type 1 and 2 expression in the human fetus.

The present study investigates the expression patterns of 17beta-hydroxysteroid dehydrogenase (17betaHSD) isozymes in human fetal tissues to understand how estrogenic activity is regulated in the human fetus. Using enzyme assay, high 17betaHSD activity was detected in the placenta and liver, and low levels of 17betaHSD activity were also present in the gastrointestinal tract and kidney. After Northern blot analysis, we detected the messenger ribonucleic acid for 17betaHSD type 1 (17betaHSD1) only in the placenta, whereas that for 17betaHSD type 2 (17betaHSD2) was detected in the placenta, liver, gastrointestinal tract, and urinary tract at 20 gestational weeks. In RT-PCR analysis of the messenger ribonucleic acid transcripts, 17betaHSD 1 was predominantly expressed in the placenta, brain, heart, lung, and adrenal, whereas 17betaHSD2 expression was predominantly detected in the liver, gastrointestinal tract, and kidney. In addition, we detected 17betaHSD2 immunoreactive protein in surface epithelial cells of the stomach, absorptive epithelial cells of the small intestine and colon, hepatocytes of the liver, and interstitial cells surrounding the urinary tubules of the renal medulla. 17betaHSD2 in these tissues may be functioning in the prevention of in utero exposure of the fetus to excessive estradiol from the maternal circulation and amniotic fluids.

17-Hydroxysteroid Dehydrogenases↗

PubMed2000

The vasocontractive action of norepinephrine and serotonin in deep arterioles of rat cerebral gray matter.

To examine the direct effects of norepinephrine (NE) and serotonin (5-HT) on the contractility of arterioles in the gray matter of the rat cerebrum, we micro-perfused arterioles in vitro and observed the changes in luminal diameter under the stop-flow condition with constant intraluminal pressure. While the average diameter of the lumen of arterioles was 39.9 +/- 9.7 microm (n=7) in Hepes-buffered saline, the average in 10(-7) M NE in the extraluminal solution changed into smaller in saline by 21.1 +/- 5.4% (n=7). The contractile effect of NE shows a dose-dependent curve between the 10(-7) and 10(-5) M. The contractile response to 10(-6) M NE was significantly reduced by yohinbin, an alpha2 blocker. 10(-6) M NE applied to the lumen also caused contraction of arterioles by 12.4 +/- 5.3% in diameter (n=5). 5-HT at 10(-7) M in the extraluminal solution caused contraction of arterioles by 10.9 +/- 4.4% in diameter (n=7). 5-HT in the extraluminal solution caused contraction of arterioles in a dose dependent manner between 10(-10) and 10(-6) M. The contractile effect of 5-HT at 10(-6) M was strongly reduced by 10(-6) M ketanserin, a 5-HT2 receptor antagonist. 5-HT applied to the lumen had no effect at all (n=6), however NE applied to the lumen caused contraction. These results strongly suggest that 5-HT plays a significant role in arteriolar contractility only from the cerebrospinal fluid (CSF) side, while NE is an important regulator of arteriolar contractility from both the CSF and blood circulation sides.

Adrenergic alpha-Antagonists↗