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Biomedical subjects

N Satake

Publications and source records attributed to N Satake.

At least 73 records · Page 4Linked to original sources
PubMed1994

Possible mechanisms of vasoinhibitory effects of mequitazine, an antiallergic agent, on the contractions of isolated rat aorta induced by K+, phenylephrine, 5-hydroxytryptamine, and Ca2+.

Mequitazine, 10-(3-quinuclidinylmethyl) phenothiazine, inhibited contractile responses to KCl, phenylephrine (PE), 5-hydroxytryptamine (5-HT), and Ca2+ in rat aorta. Indomethacin or removal of endothelium did not affect the inhibitory effect of mequitazine on the responses to PE. In Ca(2+)-free medium containing EGTA and nifedipine, mequitazine inhibited both residual response to PE and subsequent response to Ca2+ in the presence of PE. Mequitazine potentiated the relaxation to nitroglycerin (NTG) and isoproterenol. In the presence of forskolin, mequitazine did not cause further potentiation of NTG relaxation. Mequitazine relaxation was slightly inhibited by nifedipine and was potentiated by theophylline. The relaxation was not affected by zaprinast, methylene blue, W-7, propranolol, cimetidine, glyburide, or tetraethylammonium. Tissue level of cyclic AMP in rat aorta was increased by mequitazine. These results suggests that mequitazine may inhibit voltage-operated Ca2+ channels (VOC) and increases the level of cyclic AMP.

Animals↗
PubMed1994

Nephrosis augments contractile response to adrenoceptor agonists by the decrease in release of endothelium-derived relaxing factor from the endothelial cells.

The thoracic aorta was taken from nephrotic rats on the 40th day after a single i.v. injection of daunomycin (10 mg/kg). In the endothelium-intact aorta, the contractions induced by norepinephrine or B-HT 933, an alpha-2 adrenoceptor agonist, were significantly greater in nephrotic rats than in normal animals. However, such a difference was not observed in the KCl- or U46619-induced contractions. The difference in norepinephrine-induced contraction between nephrotic and normal preparations was enhanced by zaprinast, a cyclic GMP phosphodiesterase inhibitor. The contractions elicited by norepinephrine and B-HT 933 were potentiated by either removal of the endothelium or pretreatment with methylene blue, a guanylate cyclase inhibitor. The difference in the contractile response to these agonists between nephrotic and normal preparations was eliminated completely by either treatment. The cyclic GMP level in the endothelium-intact aorta in the presence of zaprinast was significantly lower in nephrotic rats than in normal animals. In the presence of zaprinast, norepinephrine, but not B-HT 933, caused an increase in the cyclic GMP level, which was abolished completely by pretreatment with prazosin, but not by yohimbine. These results suggest that the augmented contractile response to norepinephrine observed in nephrotic aorta may be due to the decrease in the stimulated release of endothelium-derived relaxing factor from the endothelial cells via the stimulation of endothelial alpha-1 adrenoceptors, whereas the augmented response to B-HT 933 may be due, at least in part, to the decrease in spontaneously released endothelium-derived relaxing factor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

TNF alpha mRNA, but not IL-1 beta, is differentially expressed in lung macrophages of patients with active pulmonary sarcoidosis.

In pulmonary sarcoidosis or experimental granuloma formation, interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) seem to play important roles during the inflammatory process. In order to examine whether IL-1 beta or TNF alpha mRNA expression in lung macrophages relates to disease activity or clinical course, ten cases with pulmonary sarcoidosis were divided into two groups: five cases with disease duration of more than 10 years (14.6 +/- 4.4 yrs; group A), and 5 cases with a duration of less than 3 years (1.7 +/- 1.1 yrs; group B). All cases showed both abnormal chest X-rays and elevated serum angiotensin converting enzyme activities. We compared these ten cases with 12 healthy subjects (6 nonsmokers: NS and 6 current smokers: S), and 5 cases with idiopathic pulmonary fibrosis (IPF) as disease control. Lavage macrophages were purified using the rosette forming method followed by plastic adhesion for one hour. Thereafter, RNA was extracted according to the AGPC method and amplified by the reverse transcription-polymerase chain reaction (RT-PCR). The results showed that IL-1 beta mRNA was detected in all samples studied, but TNF alpha mRNA expression was different among the groups: 5/5 (100%) in group A, 1/5 (20%) in group B, 5/5 (100%) in IPF, and 12/12 (100%) in healthy subjects. A constitutive expression was seen in healthy controls. On the other hand, no detection of TNF alpha mRNA was shown in pulmonary sarcoidosis. This fact may relate to a spontaneous regression of inflammation in sarcoidosis, as a substantial number of cases in group B may in time regress spontaneously.

Adult↗
PubMed1993

A Japanese family of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy.

Three cases of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy are described from one related Japanese kindred. Two boys had died due to severe diarrhoea accompanied by total or subtotal intestinal villous atrophy. In contrast, although one patient showed the same symptoms and had circulating IgG antibodies against enterocytes, his condition improved dramatically and he developed well following the use of cyclosporin A (CSA). CSA may be beneficial in patients with this rare disorder. Auto-immune enteropathy should be considered as a cause of protracted diarrhoea with unknown aetiology.

Anemia, Hemolytic↗
PubMed1993

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p- chlorobenzenesulfonylamino)-butyl]-azulene-1-sulfonic acid sodium salt); a new TXA2/prostaglandin endoperoxide receptor antagonist.

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p-chlorobenzenesulfonylamino)butyl]-azulene+ ++-1-sulfonic acid sodium salt, KT) were studied in isolated rat aorta, rat tail artery, rabbit aorta, rabbit renal artery, and pig coronary artery. KT competitively inhibited the contractions induced by thromboxane A2 (TXA2) mimetic, U46619 (pA2 values 9.95, 8.85, 7.87, 8.49, and 9.12, respectively). KT also inhibited the contraction of rabbit aorta induced by prostaglandin2 alpha (PGF2 alpha, pA2 value 7.85) and the contraction of guinea pig ileum induced by LTD4 (pA2 value 5.48) but did not alter the contractions induced by norepinephrine (NE), Ca2+, serotonin, and histamine. KT did not alter the contractions of guinea pig ileum, which did not contract with U46619, induced by PGE2 and PGF2 alpha. KT inhibited the aggregations of rabbit platelets induced by U46619, arachidonic acid, and collagen (IC50 values 7.9, 140, and 16 microM, respectively) but not those induced by ADP. It also inhibited the specific binding of TXA2/PGH2 receptor antagonist, [3H]SQ29,548, to rabbit gel-filtered platelets with an IC50 value of 1.5 x 10(-8) M. In in vivo experiments with mice, oral administration of KT protected the U46619-induced sudden death with the minimum effective dose of 0.3 mg/kg and provided such protection for > 8 h at 1.0 mg/kg. These results indicate that KT is a new nonprostanoid type TXA2/PGH2 receptor antagonist that is orally effective and long acting.

Animals↗
PubMed1993

Gastrin-releasing peptide-like immunoreactive substance in bronchoalveolar lavage of idiopathic pulmonary fibrosis and sarcoidosis.

The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.

Adult↗
PubMed1993

Density of phenotypic markers on BAL T-lymphocytes in hypersensitivity pneumonitis, pulmonary sarcoidosis and bronchiolitis obliterans with organizing pneumonia.

In vitro studies have shown that the density of surface antigens reflects the degree of activation of T-cells. We therefore studied the density of surface antigens on T-cells from bronchoalveolar lavage fluid (BALF) and blood in patients with sarcoidosis, hypersensitivity pneumonitis (HP) and bronchiolitis obliterans with organizing pneumonia (BOOP). BALF cells were stained with anti-CD3, anti-CD4, anti-CD8 and anti-human leucocyte antigen-DR(HLA-DR) monoclonal antibodies, and were analysed by cytoflowmetry. The density was evaluated by measuring the Mean Channel fluorescence intensity of the stained cells. The results demonstrated a significant increase in the CD3 density in patients with hypersensitivity pneumonitis (108.2 +/- 20.2 MC), compared with those with pulmonary sarcoidosis (51.2 +/- 12.6), BOOP (74.5 +/- 29.3), and healthy controls (57.1 +/- 11.5). Similar results were obtained for the CD4 and CD8 density in patients with HP. Although the number of HLA-DR positive cells was increased, the density was lower in patients with sarcoidosis (57.4 +/- 11.6) and hypersensitivity pneumonitis (57.4 +/- 14.8), than in healthy controls (72.2 +/- 15.1). Comparable changes were not observed in the peripheral blood. These results suggest that T-cell activation in hypersensitivity pneumonitis may be associated with an increase in the CD3, CD4, and CD8 density on BALF T-cells.

Adult↗
PubMed1992

Mode of relaxing action of FK336, a new antianginal agent, in rabbit aorta.

1. FK336 (10(-6)-10(-4) M) inhibited contractile responses to norepinephrine (NE), KCl and Ca2+ in isolated rabbit aortas. 2. Relaxing effect of FK336 on KCl-response was inhibited by nitroglycerin (NG), but not by nifedipine or verapamil. 3. FK336 inhibited residual NE response and a subsequent Ca2+ response in Ca(2+)-free medium. FK336 did not affect the inositol monophosphate level. 4. Relaxing effect of FK336 on NE response was inhibited by methylene blue, NG, K(+)-channel inhibitors and acetylcholine (ACh), and potentiated by M&B 22,948 and theophylline. 8-Br cGMP and dibutyl cAMP had no effect. 5. FK336 increased cGMP level in rat aorta. 6. Potentiation of isoproterenol-relaxation by FK336 was inhibited by methylene blue. 7. The inhibitory effect of ACh on FK336-relaxation was eliminated by endothelium removal, nordihydroquaiaretic acid and guinacrine, but not by indomethacin. These treatments themselves did not affect FK336-relaxation. 8. The mode of vasorelaxing action of FK336 is discussed.

Acetylcholine↗
PubMed1992

Characterization of IL-1 inhibitory factor released from human alveolar macrophages as IL-1 receptor antagonist.

IL-1 possesses pleiotropic properties on various cells and its activity may be stringently regulated in several ways. We have previously reported that both IL-1 and its inhibitory factor are concomitantly released from alveolar macrophages in both healthy subjects and patients with chronic inflammatory lung diseases. An increase in IL-1 activities and a decrease in inhibitory activities are characteristics found in both healthy smokers and patients with interstitial lung diseases. In this study, we further examined the biological properties of IL-1 inhibitory factor. The inhibitor exhibited a dose-dependent specific inhibition of an augmentation by IL-1 of PHA-induced murine thymocyte proliferation, while no inhibition of the augmentation by IL-2, IL-4, IL-6, or tumour necrosis factor (TNF) was found. 125I-labelled IL-1 alpha binding on PHA-stimulated murine thymocytes revealed two types of IL-1 binding sites, 44 sites/cell with a Kd of 2.7 x 10(-10) M and 230 sites/cell with a Kd of 2.5 x 10(-9) M. Alveolar macrophage culture supernatants blocked the binding of labelled IL-1 to the IL-1 receptor in a dose-dependent fashion. Scatchard plot analysis revealed that the inhibitory factor in the supernatants blocked the binding competitively. These results indicate that alveolar macrophages produce a specific IL-1 inhibitory factor, functioning as an IL-1 receptor antagonist.

Cells, Cultured↗
PubMed1992

Possible mechanisms of inhibition with atropine against noradrenaline-induced contraction in the rabbit aorta.

1. In the rabbit isolated aorta, atropine (3 x 10(-6) M-10(-4) M) inhibited contractile response to noradrenaline without affecting contraction to KCl. 2. In the presence of contraction to noradrenaline, atropine (3 x 10(-7) M-10(-4) M) caused concentration-dependent relaxation. Pretreatment with theophylline (10(-3) M) potentiated the relaxant action of atropine. Relaxation to atropine was not affected by the specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M & B 22,948 (10(-4) M), tetraethylammonium (10 mM), indomethacin (10(-5) M), propranolol (10(-7) M), nifedipine (10(-6) M) or removal of the endothelium. 3. Relaxation to either atropine or prazosin was not affected by preincubation with prazosin and atropine, respectively. 4. In Ca(2+)-free medium containing EGTA and nifedipine, atropine (10(-7) M-10(-4) M) inhibited the residual noradrenaline response more than the subsequent Ca(2+)-induced contraction. Pretreatment with either theophylline (10(-3) M), forskolin (3 x 10(-7) M) or a low concentration of prazosin (3 x 10(-9) M) also inhibited the residual contraction to noradrenaline and Ca2+. The effect of combined treatment of atropine and any of these agents was much greater than with each individual agent. 5. Atropine (10(-6) M-10(-4) M) also inhibited increases in the level of inositol monophosphates (IP) in response to noradrenaline. Theophylline (10(-3) M) and a low concentration of prazosin (3 x 10(-9) M) also inhibited IP formation. Combined with atropine, the effect was much greater than with each of these agents individually. 6. Atropine did not affect adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in the aorta and also failed to displace specific [3H]-prazosin binding.7. These results suggest the possibility that smooth muscle relaxation to atropine may be due to the inhibition of phosphoinositide metabolism. The relaxation is not apparently due to an action of atropine on ax-adrenoceptors, or a change in the level of cyclic AMP.

Animals↗
PubMed1992

Characteristics of vasoinhibitory action of FK 453 (a pyrazolo-pyridine derivative), a new antihypertensive agent with diuretic action in isolated rabbit aorta.

The vasoinhibitory effect of FK 453 was examined in isolated rabbit aorta. FK 453 inhibited contractile responses to norepinephrine, angiotensin-I and KCl. Pretreatment of the tissue with FK 453 failed to affect the relaxing effect of verapamil on the KCl response and the inhibitory effect of prazosin on the phenylephrine response. FK 453 inhibited both the residual norepinephrine response and the subsequent Ca2+ response in a Ca(2+)-free medium containing EGTA and nifedipine. The inhibitory effect of a combined treatment with either FK 453 plus nitroglycerin or FK 453 plus theophylline, but not with FK 453 plus M & B 22,948 (2-o-propoxyphenyl-8-azapurine-6-one; May & Baker), was much greater than that of any single treatment. Pretreatment with FK 453 also potentiated relaxing effects of nitroglycerin and isoproterenol on the PGF2 alpha response. The effect of a combined treatment with FK 453 plus theophylline, but not with FK 453 plus M & B 22,948, was much greater than that of any single treatment. FK 453 also inhibited the activity of phosphodiesterase from canine aorta to convert cyclic [3H]-GMP and cyclic [3H]-AMP to 5'-GMP and 5'-AMP, respectively. These results suggest that the inhibitory action of FK 453 is not due to inhibition of voltage-operated Ca2+ channels or alpha-adrenoceptors, but due to increase in cyclic GMP level.

Angiotensin I↗
PubMed1991

Pharmacological characteristics of NP-252, a new dihydropyridine slow Ca2+ channel blocker, in isolated rabbit vascular smooth muscle and guinea pig myocardium: vascular selectivity.

NP-252, a new dihydropyridine derivative, and nifedipine non-competitively inhibited contractile responses to KCl and responses to Ca2+ in Ca(2+)-free medium containing KCl in rabbit aorta and renal, mesenteric, coronary and basilar arteries, mesenteric veins and vena cava. The effects of NP-252 in these smaller arteries and veins were much greater than those in aorta. However, a similar differential selectivity was not seen with nifedipine. In aorta, only NP-252 reduced total La3+ resistant 45Ca binding. However, the increases in bound 45Ca at La3+ resistant sites and 45Ca unidirectional influx due to KCl were inhibited by both NP-252 and nifedipine. The displacement of [3H]nitrendipine binding to rabbit aorta was monophasic for both NP-252 and nifedipine. In guinea-pig papillary muscles, NP-252 (greater than 10(-7) M) slightly decreased action potential duration, developed tension and slow action potentials. The cardiac effects of NP-252 were much less prominent than those of nifedipine. These results indicate that NP-252 inhibits voltage-operated Ca2+ channels in small arteries and veins much more effectively than those in aorta, and this tissue selectivity is more apparent for NP-252 than nifedipine.

Action Potentials↗
PubMed1991

Impaired endothelium-dependent relaxation in isolated thoracic aorta of rats with daunomycin-induced nephrosis.

A single i.v. injection of daunomycin (10 mg/kg) into rats produced severe proteinuria and hypercholesterolemia without atherosclerosis on the 20th and 40th days after the treatment. However, these changes were not observed on the 5th day. No change in systolic blood pressure was seen through the 40-day experimental period. Relaxation to acetylcholine, A23187 and nitroprusside was examined in aortic rings precontracted with phenylephrine (3 x 10(-6) M). Acetylcholine-induced relaxation was significantly attenuated in the nephrotic rats on the 20th and 40th days, in comparison to the control animals. In aortic rings taken from control and nephrotic rats on the 40th day, removal of the endothelium or treatment with methylene blue (10(-5) M) completely abolished the relaxation induced by acetylcholine (10(-5) M). In addition, acetylcholine (10(-5) M) induced a transient increase in the aortic cyclic GMP and this increase was completely abolished by removal of the endothelium. In the preparations of nephrotic rats on the 20th and 40th days, the cyclic GMP levels stimulated by acetylcholine (10(-5) M) were decreased to about 50% in comparison to their respective control. A23187 also evoked diminished relaxation in nephrotic rats on the 20th and 40th days. However, on the 40th day after the treatment, the effects of nitroprusside in relaxing the aorta and in elevating the cyclic GMP level in the aorta were not altered by nephrosis. In addition, the nitroprusside-induced relaxation and cyclic GMP accumulation were not affected by removal of the endothelium. These results indicate that endothelium-dependent relaxation is attenuated with the development of nephrosis.

Acetylcholine↗
PubMed1991

The inhibitory action of okadaic acid on mechanical responses in guinea-pig vas deferens.

Okadaic acid and nifedipine inhibited contractions induced by noradrenaline (NA), KCl and ATP in guinea-pig vas deferens. NA, KCl and ATP induced initial spike-like changes followed by a sustained increase in cytosolic Ca2+ levels ([Ca2+]cyt) and tension. Okadaic acid inhibited the sustained increments in [Ca2+]cyt and muscle tension due to NA and ATP more than the initial spike-like changes, whereas nifedipine more strongly inhibited the initial spike changes. Okadaic acid also inhibited the KCl-induced contraction with only a small inhibition of the stimulated [Ca2+]cyt. By contrast, nifedipine (10(-7) M) inhibited the increments in both [Ca2+]cyt and muscle tension due to KCl. Okadaic acid markedly inhibited the maximal contractile response to Bay K 8644 but nifedipine only shifted the response curve to the right without affecting the maximum responses. In a Ca2(+)-free medium containing EGTA and nifedipine, okadaic acid did not inhibit the residual phasic contractile response to NA (10(-4) M) but the contractile response to a subsequent addition of Ca2+ (1.2 mM) was suppressed. These results suggest that, in guinea-pig vas deferens, okadaic acid has an inhibitory effect on smooth muscle contraction but not on the intracellular Ca2+ mobilization. The inhibitory effect may be due to the inhibition of Ca2+ influx and the possible interference of contractile elements.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗