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S Suga

Publications and source records attributed to S Suga.

At least 181 records · Page 10Linked to original sources
PubMed1994

Natriuretic peptide clearance receptor is transcriptionally down-regulated by beta 2-adrenergic stimulation in vascular smooth muscle cells.

Three natriuretic peptide receptors (the ANP-A, ANP-B, and clearance (C) receptors) have been reported. The regulation of these receptors by catecholamines was examined in cultured rat vascular smooth muscle cells. Treatment with norepinephrine decreased the maximum 125I-ANP binding. The competitive binding assay with des[Gln18,Ser19,Gly20,Leu21, Gly22]ANP-(4-23)-NH2 (C-ANF-4-23), a specific ligand for the C receptor, revealed that the decrease in the 125I-ANP binding by norepinephrine was caused by the down-regulation of the C receptor. Isoproterenol also down-regulated the C receptor in a time- and dose-dependent manner. The catecholamine-induced down-regulation of the C receptor was antagonized by a beta 2-selective adrenergic antagonist, ICI 118,551 but not by an alpha 1-, alpha 2-, or beta 1-adrenergic antagonist. Forskolin, NaF and, 8-bromo-cyclic AMP also decreased the C receptor density. The isoproterenol-induced decrease in the C receptor level was further confirmed by affinity cross-linking and Western blot analysis. Northern blot analysis revealed that isoproterenol and 8-bromo-cyclic AMP decreased the steady-state level of C receptor mRNA. By contrast, neither the ANP-A receptor nor the ANP-B receptor mRNA level was affected by 8-bromo-cyclic AMP. The nuclear run-on assay showed that the transcriptional rate of the C receptor gene was decreased by isoproterenol, whereas those of the ANP-A and ANP-B receptor genes were unchanged. Isoproterenol attenuated the clearance of exogenously added ANP and augmented the ANP-stimulated intracellular cyclic GMP production to the same extent as the selective occupancy of the C receptor with C-ANF-(4-23), suggesting that the isoproterenol-induced enhancement of responsiveness to ANP could result not from the sensitization of the ANP-A or ANP-B receptor but from the down-regulation of the C receptor, which leads to the attenuated clearance of ANP. These findings suggest that the beta 2-adrenergic receptor stimulation down-regulates the C receptor through the decrease in the transcriptional rate of the C receptor gene and that the activation of the sympathetic nervous system augments the biological responsiveness to natriuretic peptides by attenuating their metabolic clearance in vascular walls.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes. Induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies.

Fusion regulatory proteins (FRPs) are newly defined cell surface molecules that enhance and/or induce virus-mediated cell fusion. Anti-FRP-1 Abs reacted with all of the established cells derived from humans and monkeys, whereas FRPs were found to be selectively expressed on a fraction of monocytes in human PBMCs. Granulocytes expressed no FRP-1 molecules, but approximately 18% of granulocytes expressed FRP-2 molecules. Alveolar macrophages also expressed FRP-1 molecules. FRP-1 expression was enhanced by culture of monocytes, but CD14 expression was not influenced by cultivation. Anti-FRP-1 Abs induced homotypic cell aggregation and multinucleated giant cell formation of monocytes. Anti-beta 2 integrin Ab blocked anti-FRP-1 Ab-induced cell aggregation, and anti-beta 1 integrin Ab and fibronectin inhibited anti-FRP-1 Ab-induced polykaryocyte formation. There was no competitive binding to monocytes between anti-FRP-1 Ab and anti-beta 1 or anti-beta 2 integrin Ab or fibronectin. Furthermore, there was no enhancement of beta 1 and beta 2 integrin expression by anti-FRP-1 Ab on monocytes. These findings suggest that anti-FRP-1 Ab activated integrin systems, and that the functions of anti-FRP-1 Ab were demonstrated through the activated integrin systems. Furthermore, it is inferred that integrin systems are involved in polykaryocyte formation of monocytes.

Amino Acid Sequence↗
PubMed1994

Expression of biologically active receptors for natriuretic peptides in the human uterus during pregnancy.

Human amnion cells secrete a large amount of brain natriuretic peptide (BNP). In the present study, to elucidate the possible roles of amniotic BNP during the course of human pregnancy, the tissue distributions of biologically active receptors of natriuretic peptides, atrial natriuretic peptide (ANP)-A receptor and ANP-B receptor in the human uterus during pregnancy were investigated by Northern blot analysis and an in vitro guanosine 3',5'-cyclic phosphate (cGMP) generation assay, the second messenger of natriuretic peptides, using crude membrane preparations. Both ANP-A and ANP-B receptor mRNAs were detected in the tissues of decidua vera, chorion laeve, myometrium and placenta. The in vitro cGMP generation assay revealed that the expression of ANP-A receptor was more prominent than that of ANP-B receptor in these tissues. On the other hand, in amniotic tissue only ANP-B receptor mRNA was weakly expressed but ANP-A receptor mRNA was not detected.

Atrial Natriuretic Factor↗
PubMed1994

Functional evidence for an apical ANP receptor in LLC-PK1 kidney epithelial cells.

The localization of natriuretic peptide receptors was studied in LLC-PK1 cell monolayers grown on a micro-porous membrane filter. The addition of alpha-human atrial natriuretic peptide (alpha-hANP) to the apical side of the cells produced a concentration-dependent increase in cyclic GMP (cGMP) formation, the extent of which was similar to that produced by the addition to the basolateral side. More cGMP was formed with alpha-hANP (1 and 100 nM) than with the C-type natriuretic peptide (100 nM). These findings indicate that the biologically active receptors with high efficacy for alpha-hANP are expressed in both the apical and basolateral membranes in LLC-PK1 cells.

Animals↗
PubMed1994

Detection of C-type natriuretic peptide in human circulation and marked increase of plasma CNP level in septic shock patients.

We have previously reported that C-type natriuretic peptide (CNP), the third member of natriuretic family, was produced in vascular endothelial cells and hypothesized that CNP might be a local regulator of vascular tone and/or growth from endothelial cells. In order to clarify the pathophysiological significance of CNP in humans, we examined the presence of CNP in human circulation and determined plasma levels of CNP in patients with various cardiovascular disorders. The plasma level of CNP in healthy persons was 1.4 +/- 0.6 fmol/ml (n = 13). The plasma level of CNP was markedly increased in patients with septic shock (13.2 +/- 10.1 fmol/ml, n = 11), while there was no alteration in patients with congestive heart failure or hypertension. There was two-fold increase of the plasma CNP level in patients with chronic renal failure. These results indicate that CNP, which can be considered as an endothelium-derived relaxing peptide, is detectable in human circulation and suggest the pathophysiological significance of endothelial CNP in humans.

Aged↗
PubMed1994

Sequential change of brain edema by semiquantitative measurement on MRI in patients with hypertensive intracerebral hemorrhage.

The progression of brain edema in seven patients with hypertensive intracerebral hemorrhage (ICH) was evaluated. Five were of putaminal and two were of thalamic hemorrhage. The hematoma volume in the patients was 4 approximately 40 ml (18.9 +/- 8.0 ml). Sequential MRI (SE: 2000/40) was performed at one, two and four weeks after onset. The edema volume (EV) was calculated as 1/2.(long diameter).(short diameter).(thickness) of the high intensity area (HIA) on MRI. In comparison with the EV at one week after onset, the EV at two weeks was increased and the EV at four weeks returned to the same level of that at one week (132.3 +/- 26.1%, 100 +/- 10.6%, respectively). In contrast, the consciousness level and motor weakness of the patients had already improved at two weeks after onset. Our results demonstrate that progression of brain edema after small or medium size ICH may not bring about a deterioration of the clinical course. Moreover, progression of brain edema to the cerebral cortex and ventricle as indicated by MRI suggested an absorption pathway for the edema fluid, and implying that brain edema following ICH could play a part in the healing process after ICH.

Aged↗
PubMed1994

Effect of barrier opening on brain edema in human brain tumors.

Blood-brain barrier (BBB) opening was carried out in 10 patients with cerebral lesions, and the MRI findings were evaluated following the barrier opening. An intra-arterial injection of 10% glycerol (4 ml/kg, 1 approximately 2 ml/s) was given as a hyperosmotic solution. T2-weighted MRI was undertaken using a TOSHIBA 22A at 30 minutes after BBB opening. Barrier-opening MRI was performed 10 times in 10 patients, including 5 cases of glioblastoma multiforme, 2 cases of astrocytoma, 1 case of malignant lymphoma, 1 case of cerebral contusion and 1 case of neurinoma. The high-intensity area (HIA) was compared with that in MRI without barrier opening. Three types of changes of HIA in MRI were observed after BBB opening as follows. Type 1: Expansion of the HIA was noted in 4 of 5 cases of glioblastoma multiforme, the 1 case of malignant lymphoma and the 1 case of cerebral contusion. Type 2: Almost no change was observed in the 1 case of neuronoma. Type 3: A decrease in HIA was noted in the 2 cases of astrocytoma and in 1 case of glioblastoma multiforme. The MRI following BBB opening evidently showed 3 types of changes according to the degree of BBB disruption. Glioblastoma multiforme or contusion with a severely disrupted BBB revealed an increase in HIA following barrier opening. Benign posterior fossa neurinoma showed no change in HIA after barrier opening. Moderate malignant tumors exhibited a decrease in HIA on barrier-opening MRI. It was concluded that malignant tumors have a severely damaged BBB, which is readily disrupted by osmotic barrier opening.

Adult↗
PubMed1994

Estrogen reduces the excitability of the female rat medial amygdala afferents from the medial preoptic area but not those from the lateral septum.

Electrical stimulation of the medial amygdala (AMY) elicited antidromic action potentials in neurons in the preoptic area (POA) and the lateral septum (LS) of 36 urethane-anesthetized ovariectomized female rats, which were either treated with estrogen o not treated. The extracellular potentials from the two sites showed similar characteristics, with the exception of the sensitivity to estrogen: they had latencies between 3 and 35 ms. Thresholds were as low as 100 microA. The mean relative refractory period was 2.2 ms. The peak-to-peak amplitudes of the positive-negative biphasic potential ranged from 1.0 mV to 12.0 mV. Estrogen had site-specific effects on parameters of antidromic activation in the POA. Estrogen-treated rats had a significantly higher threshold (937 vs 664 microA) and a longer refractory period (2.5 vs 2.1 ms) than the ovariectomized rats (P < 0.05 for each). The effects were absent in the LS. Selective cutting of the stria terminalis diminished the AMY-induced antidromic responses in the POA and LS. Electrical stimulation of the stria blocked the AMY-induced antidromic potentials by collision. Thus, estrogen-sensitive POA efferents as well as non-estrogen-sensitive LS efferents project to the AMY via the stria terminalis. Reductions in axonal excitability would inhibit neural conduction and transmission. Estrogen may therefore reduce the AMY inputs from the POA, without affecting those from the LS. Such alterations in the neural impulse flow may underlie estrogen-dependent neuroendocrine or behavioral regulation.

Amygdala↗
PubMed1994

Dihydrotestosterone-sensitive neurons in the male rat ventromedial hypothalamus.

Electrical stimulation of the midbrain central gray caused antidromic activation in 273 neurons in and around the hypothalamic ventromedial nucleus in 40 urethan-anesthetized male rats. The latency (range: 2-39 ms) and threshold (100-1,600 microA) of the responses were compared among intact males and orchidectomized males, which received either no treatment, daily injections of testosterone propionate or dihydrotestosterone, or a combined estradiol benzoate and progesterone injection. Recordings were from comparable neuronal pools, because probability distribution for the latency as well as histological localization of each response were not different among groups. Orchidectomy decreased the mean threshold, and either treatment reversed the effect. Dihydrotestosterone increased the mean threshold by reducing the number of cells with thresholds below 600 microA, to a level as in intact males. Estrogen reduced the number of cells responding at 300-900 microA, but at lower thresholds, fell short of replicating the distribution in intact males. Testosterone reinstated the distribution as in intact males. It was concluded that different subgroups of ventromedial hypothalamic neurons with specific sensitivity to metabolites of testosterone project to the central gray.

Action Potentials↗
PubMed1994

Endoscopic ultrasonography with color Doppler function in the diagnosis of rectal variceal bleeding.

Extraesophagogastric variceal bleeding in patients with portal hypertension is rare, but has been reported after endoscopic injection sclerotherapy (EIS) for esophageal varices. Here, we report rectal variceal hemorrhage following EIS. Endoscopic ultrasonography with color Doppler function (EUSCD) was useful for the diagnosis of rectal varices and complete hemostasis was obtained with EIS. A review of the literature since 1980 revealed a total of 15 patients, including ours, with extraesophagogastric variceal bleeding following EIS. This suggests EIS is the principal emergency treatment for bleeding rectal varices.

Endoscopy, Gastrointestinal↗
PubMed1994

Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene.

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle. To study the roles of BNP in chronic cardiovascular regulation, we isolated mouse BNP cDNA and genomic clones, and generated transgenic mice with elevated plasma BNP concentration. The mouse BNP gene was organized into three exons and two introns. Two BNP mRNA species were identified, which were generated by the alternative mRNA splicing. The ventricle was a major site of BNP production in mice. Mouse preproBNP was a 121- (or 120-) residue peptide, and its COOH-terminal 45-residue peptide was the major storage form in the heart. Transgenic mice carrying the human serum amyloid P component/mouse BNP fusion gene were generated so that the hormone expression is targeted to the liver. In the liver of these mice, considerable levels of BNP mRNA and peptide were detected, reaching up to 10-fold greater than in the ventricle. These animals showed 10- to 100-fold increase in plasma BNP concentration accompanied by elevated plasma cyclic GMP concentration, and had significantly lower blood pressure than their nontransgenic littermates. The present study demonstrates that these mice provide a useful model system with which to assess the roles of BNP in cardiovascular regulation and suggests the potential usefulness of BNP as a long-term therapeutic agent.

Alternative Splicing↗
PubMed1994

Molecular cloning of hamster brain and atrial natriuretic peptide cDNAs. Cardiomyopathic hamsters are useful models for brain and atrial natriuretic peptides.

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.

Amino Acid Sequence↗