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H Kase

Publications and source records attributed to H Kase.

At least 73 records · Page 4Linked to original sources
PubMed1992

Differences in activities of thromboxane A2 receptor antagonists in smooth muscle cells.

Thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors were characterized in rat vascular smooth muscle cells (VSMC). The specific binding of [3H]SQ 29,548 was inhibited by KW-3635, a novel non-prostanoic TXA2 antagonist, SQ 29,548 and BM-13505 (daltroban). SQ 29,548 showed a single class of binding sites with a Ki value of 1.6 nM. The inhibition patterns were better fit to two-component curves for KW-3635 (Ki values of 0.45 nM and 42 nM) and BM-13505 (2.3 nM and 20 nM). U46619, a TXA2 agonist, induced an increase in intracellular calcium concentration ([Ca2+]i), which was inhibited by these antagonists. KW-3635 and SQ 29,548 did not induce any increase in [Ca2+]i, whereas BM-13505 was found to induce a smaller increase in [Ca2+]i. The BM-13505-induced increase in [Ca2+]i was also inhibited by pretreatment with KW-3635, SQ 29,548 and BM-13505. The results demonstrate that BM-13505 has partial agonistic activity on TXA2/PGH2 receptors, and KW-3635 and SQ 29,548 do not. SQ 29,548 and BM-13505 inhibited both U-46619- and BM-13505-induced increases in [Ca2+]i to a similar degree. Alternatively, KW-3635 inhibited a U46619-induced increase in [Ca2+]i more effectively than a BM-13505-induced increase. These results suggest the heterogeneity of functional binding sites or subtypes of TXA2/PGH2 receptors present in VSMC.

Animals↗
PubMed1992

HS-142-1, a novel nonpeptide atrial natriuretic peptide (ANP) antagonist, blocks ANP-induced renal responses through a specific interaction with guanylyl cyclase-linked receptors.

HS-142-1, a novel microbial product, blocked 125I-labeled rat atrial natriuretic peptide (rANP) (= ANF(99-126)) binding to bovine adrenocortical membranes, where guanylyl cyclase-containing receptors are predominantly expressed. However, HS-142-1 only slightly inhibited [125I]rANP binding to bovine lung membranes where only a small portion of binding sites are coupled to guanylyl cyclase. Further, HS-142-1 only recognized the 135 kDa ANP receptor, which is considered to be the guanylyl cyclase-containing receptor based on the results obtained in affinity cross-linking studies with bovine adrenocortical and lung membranes. Under identical conditions, Atriopeptin I selectively recognized guanylyl cyclase-free receptors both in binding and affinity cross-linking experiments. When injected intravenously (1 mg/kg) to anesthetized rats, HS-142-1 abolished ANP-induced diuresis and natriuresis. These results suggest that HS-142-1 works in vivo through a specific interaction with the ANP functional receptor, and that HS-142-1 will be a powerful tool for understanding the physiological roles of ANP in distinction from its pharmacological effects.

Adrenal Glands↗
PubMed1992

Wortmannin, a microbial product inhibitor of myosin light chain kinase.

We have found that a fungal strain, Talaromyces wortmannin KY12420, produces a potent inhibitor of smooth muscle myosin light chain kinase (MLCK). This active product, designated as MS-54, was isolated and purified from the culture broth of the fungus and identified as wortmannin. The inhibition of MLCK by wortmannin was prevented by a high concentration of ATP. The activity of the catalytic domain, which was disclosed by partial tryptic digestion, was also inhibited by wortmannin. These results suggest that wortmannin acts at or near to the catalytic site of the enzyme. It was shown clearly by kinetic analyses, preincubation studies, and dialysis experiments that the inhibitory action of wortmannin on MLCK was irreversible. Under the condition of preincubation for 3 min, 0.3 microM wortmannin inhibited the activity of MLCK, while 10 microM wortmannin had no effect on the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and calmodulin-dependent protein kinase II, and had little effect on protein kinase C activity. These data expressed clearly the marked selectivity of the compound for MLCK. Furthermore, wortmannin also inhibited both the phosphorylation of myosin light chain and the contraction in rat thoracic aorta stimulated with KCl, which indicates the effectiveness of the compound in the cellular level as an MLCK inhibitor.

Adenosine Triphosphate↗
PubMed1992

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion.

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

KS-505a, a novel inhibitor of bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase from Streptomyces argenteolus.

A novel compound, KS-505a was isolated from the culture broth of a strain identified as Streptomyces argenteolus A-2. The compound inhibited bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase with an IC50 value (the concentration causing 50% inhibition) of 0.065 microM. The compound around that concentration had little or no effect on heart calmodulin-dependent and -independent cyclic-nucleotide phosphodiesterases, and protein kinase C.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Antiinflammatory effect of a protein kinase C inhibitor (K-252a) on the development of the dextran-induced paw edema in the rat (preliminary results).

The effect of a metabolite of Nocardiopsis sp. as a protein kinase C inhibitor from microbial origin was investigated on the onset and development of dextran-induced paw edema in the rat. It was published that this compound (K-252a) interferes with histamine release from mast cells, while dextran-induced paw and nose edema are induced by vasoactive agents, like histamine etc., released from the disrupted mast cells. The antiinflammatory effect of the K-252a is effectuated by the inhibition of protein kinase C. Groups of male Wistar rats with 180-200 g b.w. were used; each group consisted of 10-10 rats. The following groups were consisted: rats given orally DMSO (control), rats given 1 mg/kg, or 3 mg/kg b.w. of K-252a dissolved in DMSO and given p.o. one hour before dextran injection. Dextran (BDH Chem. LTD, molW: 200.000, England) was injected intraperitoneally in 10% solution, in a dose of one ml/100 g b.w. Volume of the hind leg was measured by a mercury plethysmometer. Time-sequence of the edema was followed. Increase in volume of hind leg paw was related to its 0-min volume in %. Results were analyzed by the Kruskal-Wallis-test. Edema of the legs and noses appeared in each of the control rats in one hour. The 1 mg/kg dose of K-252a retarded the appearance of the edema by 1 hour, the 3 mg/kg dose, however, prevented its onset for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor.

During the search for ANP receptor ligands of microbial origin, we isolated a novel polysaccharide, HS-142-1, from culture broth of Aureobasidium sp. HS-142-1 inhibited [125I]-rANP binding to ANP receptor in rabbit kidney cortex membranes with an IC50 of 0.3 mu g/ml, but gave no effects on specific binding of [125I]-Endothelin nor [125I]-Angiotensin II to their respective receptors in bovine lung membranes. HS-142-1 competitively and selectively inhibited ANP binding to its guanylyl cyclase-containing receptor purified from solubilized bovine adrenocortical membranes and blocked cGMP production elicited by ANP. HS-142-1 is the first non-peptide antagonist selective for ANP functional receptor and will be a powerful tool to elucidate the physiological functions of ANP.

Adrenal Cortex↗
PubMed1991

Differential effects of protein kinase inhibitors on pre-established long-term potentiation in rat hippocampal neurons in vitro.

The possibility that a permanent protein kinase C (PKC) activity is necessary for the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the potent kinase inhibitors K-252a, K-252b and staurosporine on LTP of orthodromic population excitatory postsynaptic potentials (EPSPs) recorded from CA1 pyramidal cells was tested both during tetanization and after establishment of LTP. Confirming earlier studies, all inhibitors applied during tetanization at a concentration of 50 nM eliminate late LTP. Only staurosporine, but not K-252a or K-252b, blocked already established late LTP (i.e. late application). Normal synaptic transmission was influenced only weakly by staurosporine. Considering that all inhibitors have similar potencies against PKC and were all effective if applied during tetanization these data suggest that the late maintenance of LTP depends on a staurosporine/H7-sensitive process (or kinase) rather than permanent activation of PKC.

Alkaloids↗
PubMed1991

Stimulatory and inhibitory actions of VIP and cyclic AMP on cytoplasmic Ca2+ signal generation in pancreatic acinar cells.

In pancreatic acinar cells the effects of vasoactive intestinal polypeptide (VIP) and dibutyryl cyclic AMP (dbcAMP) alone and during stimulation with acetylcholine (ACh) or internally applied inositol trisphosphate (InsP3) were investigated utilizing the patch-clamp whole-cell current recording configuration to assess changes in cytoplasmic Ca2+ concentration by measurement of Ca2+ dependent Cl- current. VIP (1 nM) and dbcAMP (0.5 mM) each evoked repetitive pulses of Ca(2+)-dependent Cl- current. A high VIP concentration (100 nM) acutely and reversibly inhibited the responses evoked by 1 nM VIP and also acutely inhibited ACh-evoked responses. DbcAMP (2 mM) also reversibly inhibited the ACh-evoked responses. Neither VIP nor dbcAMP were able to inhibit InsP3-evoked repetitive Ca2+ pulses. VIP in a low concentration can generate cytosolic Ca2+ oscillations via cyclic AMP, but high VIP concentrations inhibit both ACh and VIP-evoked Ca2+ signals and this effect is mediated by high intracellular cyclic AMP levels.

Acetylcholine↗
PubMed1991

Cytoplasmic Ca2+ signals evoked by activation of cholecystokinin receptors: Ca(2+)-dependent current recording in internally perfused pancreatic acinar cells.

The effects on the cytosolic Ca2+ concentration of activating cholecystokinin receptors on single mouse pancreatic acinar cells have been investigated using patch-clamp whole-cell recording of Ca(2+)-dependent Cl- current. We used the nonsulphated octapeptide of cholecystokinin (CCK8-NS) since the effects of even high concentrations were rapidly reversible which was not the case for the sulphated octapeptide. A submaximal concentration of CCK8-NS (10 nM) evoked a current response consisting of short-lasting (a few seconds) spikes, and some of these spikes were seen to trigger larger and longer (about half a minute) current pulses. At a higher concentration (100 nM) CCK8-NS evoked smooth and sustained responses. The effect of CCK8-NS was almost abolished when the internal perfusion solution contained a high concentration of the Ca2+ chelator EGTA (5 mM). The responses evoked by CCK8-NS were independent of the presence of Ca2+ in the external solution at least for the first 5 min of stimulation. Internal perfusion with GTP-gamma-S markedly potentiated the effect of CCK8-NS or at a higher concentration itself induced responses very similar to those normally evoked by CCK8-NS. Caffeine added to the external solution at a low concentration (0.2-1 mM) enhanced weak CCK8-NS responses, whereas high caffeine concentrations always inhibited the CCK8-NS-evoked responses. These inhibitory caffeine effects were quickly reversible. Forskolin evoked a similar inhibitory effect. Intracellular heparin (200 micrograms/ml) infusion markedly inhibited the response to CCK8-NS stimulation. We conclude that the primary effect of activating CCK receptors is to induce inositoltrisphosphate (IP3) production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Assay of myosin light chain kinase activity by high-performance liquid chromatography using a synthetic peptide as substrate.

The most popular method to determine the activity of myosin light chain kinase is to measure the radioactivity incorporated from [gamma-32P]ATP into phosphoryl-accepting substrates. In this paper, we report a new method for determination of myosin light chain kinase activity without using radioisotopes. Synthetic peptides and nonradiolabeled ATP were used as substrate, and the peptide substrate was phosphorylated by myosin light chain kinase purified from chicken gizzard. After terminating the reaction, the reaction mixture was directly injected into a reversed-phase HPLC column without pretreatment, separated with the isocratic solvent system of acetonitrile-H2O-trifluoroacetic acid, and monitored at 220 nm uv absorbance. The reaction rate was determined from the peak areas of phosphorylated and unphosphorylated peptides. One chromatographic separation was achieved within 9 min, and the analysis could be repeated successively more than 100 times without washing the column. Using this method, we measured the differential inhibition of myosin light chain kinase by various inhibitors. With the aid of an automatic injector, the HPLC method with synthetic peptide enables us to handle many samples quickly and is useful for screening new myosin light chain kinase inhibitors.

Adenosine Triphosphate↗
PubMed1991

[Clinical application of extracorporeal shock wave lithotripsy to 5 solitary kidney patients with upper urinary tract stones].

We performed extracorporeal shock wave lithotripsy (ESWL) to 5 solitary kidney patients with upper urinary tract stones (4 kidneys and 1 lower ureter) using the EDAP lithotripter LT-01 and achieved 4 complete and 1 well results. The size of stones ranged from 8 mm to staghorn and trials were 1 to 10 units. We could accomplish perfect crushing and abortion of stones in the 4 renal stone patients without any adjuvant systems as ureteral stent but nephrostomy was needed in the 1 lower ureteral stone patient developed anuria. The values of blood pressure, hematology, blood chemical constituents and urine excretion enzymes at a month after the last ESWL were not so changed compared with those of preoperation and also excretory urogram showed favorable findings. In this series decreased renal functions by ESWL were not observed. We confirmed ESWL was an effective and a safe method even in the cases of solitary kidney patients and monotherapy without any adjuvants was possible.

Adult↗
PubMed1990

Inhibition by new anthraquinone compounds, K-259-2 and KS-619-1, of calmodulin-dependent cyclic nucleotide phosphodiesterase.

K-259-2 and KS-619-1, novel anionic anthraquinone metabolites isolated from culture broth of microorganisms, inhibited activation of bovine brain phosphodiesterase induced by calmodulin (CaM), sodium oleate, or limited proteolysis with almost equal potency. The inhibition of calmodulin-activated phosphodiesterase (CaM-PDE) by K-259-2 or KS-619-1 was overcome by a higher concentration of CaM. Direct interaction of K-259-2 and KS-619-1 with CaM was confirmed through use of hydrophobic fluorescent probes. Kinetic analysis revealed that the inhibition of the trypsin-activated phosphodiesterase was competitively inhibited by K-259-2 or KS-619-1 with respect to cAMP. Addition of a lower amount of either phosphatidylserine or sodium oleate to the reaction mixture was efficacious in attenuating the inhibition of the CaM-PDE by W-7, chlorpromazine, trifluoperazine, compound 48/80, or R-24571 but, in contrast, had little or no effect on the inhibition by K-259-2 or KS-619-1. In conclusion, K-259-2 and KS-619-1, unlike so-called CaM antagonists, do not interact with phosphatidylserine or sodium oleate and it appears that these novel anthraquinone compounds inhibit the enzyme not only via CaM antagonism but possibly also by interacting directly with the enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Activation of a K-252b-Sensitive Protein Kinase is Necessary for a Post-Synaptic Phase of Long-Term Potentiation in Area CA1 of Rat Hippocampus.

K-252b, a potent inhibitor of protein kinases blocked a late phase of long-term potentiation (LTP) in area CA1 of rat hippocampal slices, resulting in decremental LTP. It also prevented the slowly developing increase in sensitivity of CA1 neurons to iontophoretically administered alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) which was seen in control slices that exhibit nondecremental LTP. However, K-252b applied 60 - 180 min after the induction of LTP had no effect on the potentiated synaptic and AMPA-induced responses. A K-252b-sensitive protein kinase may therefore be involved in a slowly developing postsynaptic component of LTP.

Journal Article↗
PubMed1990

Calmodulin antagonistic action of KS-504a, a novel metabolite of the fungus Mollisia ventosa.

KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) with an IC50 value of 122 microM. The inhibition was reversed by a high concentration of calmodulin. Calmodulin-independent activities of the enzyme were not affected by the compound at the same concentration ranges. Ca2(+)-dependent interaction of the compounds with calmodulin was shown using hydrophobic fluorescence probes. These data indicated that the compound exerted its effects on CaM-PDE by interacting with calmodulin. KS-504a also inhibited other calmodulin-dependent enzymes at different concentration ranges; myosin light chain kinase was inhibited at the lowest concentrations with an IC50 value of 6.3 microM. The inhibition mechanism was competitive with respect to calmodulin and non-competitive to ATP.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

[Effect of extracorporeal shock wave lithotripsy on renal function-an experience with the new type piezoelectric lithotripter, Therasonic].

Seventeen patients with renal stones and 17 patients with ureteral stones were treated using the newly developed piezoelectric shock wave lithotripter, THERASONIC. To determine the effect of shock wave on renal function, urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, urinary beta 2 microglobulin (BMG) concentration, serum BMG concentration and creatinine clearance (Ccr) were measured. Urinary NAG activity and urinary BMG concentration in renal stone patients were significantly elevated immediately after the treatment and returned to the pretreatment value within 24 hours. Neither serum BMG nor Ccr showed significant change in any of the patients. Therefore, we conclude that the renal tubular damage, which is transient and subtle, is the effect of shock wave lithotripsy using THERASONIC machine.

Acetylglucosaminidase↗
PubMed1990

[Treatment of urinary stones with Therasonic, the third generation piezoelectric shock wave lithotripter].

The THERASONIC lithotripsy treatment system, a newly developed piezoelectric lithotripter, uses both an X-ray and ultrasound system and enables stone localization effective. Treatment of urinary stones with THERASONIC was begun in June, 1989 and 57 treatments have already been performed on 38 patients. Successful treatment, defined as either stone free or with a residual stone less than 4 mm in diameter on flat X-ray film, was accomplished in 95% of the renal stones and over 50% of the ureteral stones. The overall success rate was 74%. Blood pressure and laboratory values did not show any significant change during or after the treatment. No major complication has been observed except for one perirenal hematoma which was resolved with conservative therapy.

Adolescent↗