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H Ohshika

Publications and source records attributed to H Ohshika.

At least 91 records · Page 5Linked to original sources
PubMed1990

Membrane viscosity correlates with alpha 1-adrenergic signal transduction of the aged rat cerebral cortex.

We investigated, using adult (2-month-old) and senescent (12- and 24-month-old) rats, the effects of aging on the relationship between the alpha 1-adrenergic coupling system and the membrane viscosity of the cerebral cortex. There was no age-related difference in the KD values of [3H]prazosin binding on the membranes. The Bmax values of [3H]prazosin binding were reduced with advanced age. Norepinephrine-induced formation of 3H-labeled inositol phosphates (3H-IPs) in the slices increased with advanced age. The EC50 values for norepinephrine to stimulate the formation of 3H-IPs at advanced age were lower than that at adult age. The cholesterol content in membranes increased with advanced age. No changes in the phospholipid content in membranes were observed with advanced age. Concomitantly, an increase of the molar ratio of cholesterol to phospholipids was observed with advanced age. The membrane viscosity as measured by 1,6-diphenyl-1,3,5-hexatriene increased with advanced age. These results indicate that the altered cholesterol content and/or viscosity in cortical membranes of the aged rat may account for the loss of alpha 1-adrenergic receptor density and/or compensatory changes in the receptor-phospholipase C coupling system.

Aging↗
PubMed1990

Enhancement in beta-adrenergic responsiveness of adenylate cyclase in rat liver during regeneration after carbon tetrachloride administration.

The increased ability of rat liver to respond to beta-adrenergic stimulation has been reported under several conditions which are generally associated with enhanced proliferation of hepatocytes. In the present study we examined beta-adrenergic responsiveness of adenylate cyclase (AC) during liver regeneration after carbon tetrachloride (CCl4) intoxication. Cyclic AMP accumulation in response to isoproterenol was significantly enhanced in the liver at 48 hours after CCl4 administration. Isoproterenol-stimulated AC activity was also potentiated in crude membranes from CCl4-treated rats. Beta-adrenergic receptor density and dissociation constant, estimated from Scatchard analysis of [125I]iodopindolol binding, were unchanged in membranes from control and CCl4-treated rats. AC activity stimulated with 5'-guanylyl imidodiphosphate (GppNHp) or NaF was augmented in the intoxicated rats. Furthermore, the concentration of GppNHp required for half-maximal activation (EC50) of the enzyme was significantly decreased in CCl4-treated rats. The MnCl2-stimulated activity in CCl4-treated rats did not differ from that in control. There was no appreciable difference between the pattern of autoradiographs of ADP-ribosylation by pertussis toxin or cholera toxin obtained from control and that from CCl4-treated rats. These data indicate that the ability of AC in response to beta-adrenergic stimulation in rat liver is enhanced during the process of regeneration after CCl4 treatment and that the increased function of Gs protein possibly participates in the potentiation of the responsiveness of AC.

Adenylyl Cyclases↗
PubMed1990

[Effects of calcium antagonists or beta-blockade on left ventricular diastolic function in essential hypertension].

This study was performed to assess the effect of a calcium channel blocker (nifedipine) and beta-blockade (atenolol) on left ventricular early diastolic function and filling in essential hypertension (WHO stage I, II; HT). Twenty-two untreated patients were randomly divided as nifedipine (11 patients) and atenolol (11 patients) treatment groups and both the groups had complete echocardiographic and Doppler studies. Twenty normotensive cases served as controls. Clinical and echo-Doppler data obtained at baseline and four weeks after initiation of each therapy showed no difference between the two HT groups as to mean blood pressure (before therapy, 119 +/- 3 vs 117 +/- 11 mmHg; after therapy, 106 +/- 3 vs 110 +/- 3 mmHg), left ventricular dimension, left atrial dimension, and wall thickness. To evaluate early diastolic function, the interval from the aortic closure sound (IIA, phonocardiography) to the opening of the mitral valve (MVO, echocardiography) and that from MVO to the O point of the apexcardiogram were measured. The IIA-O interval was also calculated. The peak velocities in the rapid filling (R) and atrial contraction phases (A) were measured using pulsed Doppler echocardiography at the center of the mitral orifice. The MVO-O/IIA-MVO and A/R ratios were also calculated. Compared with the controls, the IIA-O interval (143.9 +/- 6.8 msec) and the IIA-MVO interval (81.5 +/- 4.9 msec) were significantly prolonged in HT (p less than 0.01). There was no significant difference between the MVO-O interval and R. Velocity A (54.2 +/- 2.7 cm/sec) and the A/R ratio (1.01 +/- 0.11) increased significantly in HT (p less than 0.05). The IIA-O interval (before therapy, 153.3 +/- 7.6 vs after therapy, 134.3 +/- 6.2 msec) and IIA-MVO interval (87.3 +/- 6.3 vs 77.8 +/- 5.9 msec) decreased and R (43.7 +/- 3.8 vs 49.1 +/- 3.0 cm/sec) increased significantly with nifedipine. The IIA-O interval (135.7 +/- 11.3 vs 150.4 +/- 7.6 msec) and the MVO-O (58.4 +/- 3.9 vs 66.5 +/- 4.7 msec) interval were significantly prolonged with atenolol, however the IIA-MVO interval, R, and A/R did not change. A (57.5 +/- 4.0 vs 50.2 +/- 2.9 cm/sec) was also significantly decreased with atenolol. There was a significant correlation between reduction in velocity A and prolongation in the MVO-O interval (r = -0.62, p less than 0.05) with atenolol. These results suggested that the prolongation of the diastolic closure rate of the mitral valve by atenolol was related to increased ventricular filling and decreased atrial contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

[Effects of ethanol on GTP binding protein function in rat cerebral cortex: strain difference between Wistar and Fischer 344 rats].

The effect of ethanol on GTP-binding protein of cortical adenylate cyclase (AC) system in the Wistar and Fischer 344 rats was examined. In both Wistar and Fischer 344 rats, ethanol (100mM) potentiated Gpp (NH) p-stimulated AC activity and decreased EC50 for Gpp (NH)p in the cerebral cortical membrane (CCM). Ethanol treatment also augmented Mn-stimulated AC activity in Wistar CCM, whereas there was no significant change in Fischer 344 CCM. IC50 calculated from the Gpp (NH)p (0.01-0.3 microM) inhibition of forskolin-stimulated AC was decreased by ethanol treatment in Wistar CCM, but this was not the case in Fischer 344 CCM. There was no appreciable change in ADP-ribosylation of Gs and Gi in CCM with pertussis or cholera toxin. These results suggest that ethanol in vitro enhances the Gi function as well as affecting the Gs function in Wistar rat cortical AC system, and the effect of ethanol on Gi protein are different in Wistar and Fischer 344 CCM.

Adenylyl Cyclases↗
PubMed1989

Age-related changes in [3H]prazosin binding and phosphoinositide hydrolysis in rat ventricular myocardium.

1. We investigated, using rats at 2, 12 and 24 months of age, the effect of aging on ventricular alpha 1-adrenoceptor responsiveness by measuring the [3H]prazosin binding, [3H]inositol phosphate formation, the cholesterol/phospholipid ratio and membrane viscosity. 2. The density of specific [3H]prazosin binding sites on membranes was significantly reduced with advanced age, and the binding affinity for [3H]prazosin was significantly increased. 3. Norepinephrine (NE)-induced formation of [3H]inositol phosphates in slices was also reduced with advanced age. However, the EC50 for NE stimulation of [3H]inositol phosphates was significantly higher when compared to those at adult ages. 4. The cholesterol content in membranes was significantly decreased with advanced age; concomitantly, a decrease in the cholesterol/phospholipid ratio was observed. The membrane viscosity as measured by using 1,6-diphenyl-1,3,5-hexatriene significantly decreased with advanced age. 5. These results suggest that the altered cholesterol/phospholipid ratio and/or the membrane viscosity during aging may account for the increase in the binding affinity for [3H]prazosin and/or the reduced responsiveness of aged ventricular myocardium to NE.

Aging↗
PubMed1988

High K+ elevates cytosolic free Ca concentration due to mobilization from internal storage sites in rat parotid cells.

1. Effects of high K+ on cytosolic free Ca concentration ([Ca2+]i) in rat parotid cells were studied using quin2. 2. High K+ elevated [Ca2+]i in a dose-dependent manner in normal and Ca-free media. The elevation of [Ca2+]i induced by high K+ was less in the latter medium. 3. High K+ depolarized the membrane in a dose-dependent manner in normal and Ca-free media. 4. Although monensin increased [Ca2+]i, high K+ did not affect 22Na uptake into cells. 5. After treatment with oligomycin, high K+ but not carbachol raised [Ca2+]i. 6. We suggest that high K+ increases [Ca2+]i due to mobilizing Ca2+ from the intracellular storage site which does not need energy.

Amylases↗
PubMed1987

Effects of Ca2+ agonist and antagonists on cytosolic free Ca2+ concentration: studies on Ca2+ channels in rat parotid cells.

1. Effects of Ca2+ agonist and antagonists on cytosolic free Ca2+ concentration [( Ca2+]i)were studied using quin2. 2. Nicardipine (NIC), diltiazem (DIL) and verapamil (VER) had no effect on the rise in [Ca2+]i evoked by carbachol. Methoxamine-elevated [Ca2+]i was inhibited by VER but not by NIC and DIL. 3. All Ca2+ antagonists tested produced a decline of [Ca2+]i elevated by isoproterenol to the resting level. 4. The addition of 30 mM K+ gradually elevated [Ca2+]i in normal and Ca2+-free media, but it did not increase 45Ca2+ uptake into cells. BAY K 8644 did not increase [Ca2+]i. 5. We suggest that voltage-sensitive Ca2+ channels are lacking and that at least 2 distinct receptor-operated Ca2+ channels exist in rat parotid cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4,5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride-induced liver injury.

The effects of 8-(2-dimethylaminoethyl)-3-oxo-4-phenyl-1-thia-4,8-diazaspiro [4, 5] decane dihydrochloride monohydrate (Y-8845) on carbon tetrachloride (CCl4)-induced liver injury were investigated in rats. CCl4-induced attenuation of the plasma cyclic AMP (cAMP) response to glucagon stimulation was significantly prevented by pretreatment with Y-8845. Y-8845 also effectively suppressed the increases in the activities of serum transaminases as well as the decreases in microsomal glucose-6-phosphatase activity and microsomal cytochrome P-450 concentrations induced by CCl4. In rats at 72 hr after CCl4 administration, the plasma cAMP response to glucagon, microsomal glucose-6-phosphatase activity and P-450 concentration were all below the control level. Y-8845 treatment after CCl4 administration rectified these reductions to nearly normal levels. Furthermore, Y-8845 stimulated DNA synthesis during liver regeneration after CCl4 intoxication. These results demonstrate that Y-8845 has a protective effect against CCl4-induced injury in the liver and a stimulating effect on the recovery of the damaged liver.

Alanine Transaminase↗
PubMed1986

Effects of isoproterenol pretreatment on phosphatidylinositol turnover in rat parotid gland.

The effects of isoproterenol pretreatment on phosphatidylinositol turnover in rat parotid slices were studied to elucidate the relationship between beta- and alpha 1-adrenoceptors. 32P-Labeling of phosphatidylinositol in parotid slices was increased by an alpha 1- and alpha 2-agonist (epinephrine and norepinephrine) and alpha 1-agonists (methoxamine and phenylephrine), but not by an alpha 2-agonist (clonidine) and a beta-agonist (isoproterenol). Prazosin inhibited the increase in phosphatidylinositol turnover elicited by epinephrine, but propranolol did not. These results indicate that the stimulation of phosphatidylinositol turnover elicited by adrenergic agonists is mediated by activation of alpha 1-adrenoceptors in the parotid glands. Isoproterenol pretreatment of the parotid slices caused a significant increase in 32P-labeling of phosphatidylinositol and a decrease in that of phosphatidic acid. The epinephrine- or phenylephrine-induced increase in 32P-labeling of phosphatidylinositol were further enhanced by the isoproterenol pretreatment of the slices. In the isoproterenol-treated membranes of the parotid glands, [3H]prazosin binding to alpha 1-receptors increased, but [3H]dihydroalprenolol binding to beta-receptors did not. These findings indicate that the acceleration of phosphatidylinositol turnover induced by the isoproterenol pretreatment may be associated with an increase in alpha 1-adrenoceptor binding sites which might have appeared as a result of the isoproterenol pretreatment of the parotid slices.

Animals↗
PubMed1985

Contribution of extracellular and intracellular calcium to the enhanced effect of an alpha-adrenergic agonist on amylase release from dispersed rat parotid cells.

The role of calcium in the potentiation of amylase release by the alpha-adrenergic agonist methoxamine (MTX) was examined using dispersed rat parotid acinar cells. The stimulatory effect of MTX (10 microM) on the beta-adrenergic agonist isoproterenol (ISP, 1 microM)-induced amylase release was blocked by the alpha-adrenergic antagonist phentolamine (10 microM). In Ca-free (1 mM EGTA) medium, the increment of amylase release by MTX in normal medium was decreased by about 70%, but MTX still potentiated ISP-induced amylase release. MTX did not affect the cyclic AMP accumulation activated by ISP in either normal or Ca-free medium. MTX enhanced the ISP-stimulated uptake and efflux of 45Ca2+. These results suggest that both extracellular Ca2+ and intracellular stored Ca2+ may play an important role in the potentiation of amylase release from rat parotid acinar cells.

Amylases↗
PubMed1985

Beta 1-adrenoceptor-mediated amylase release and cyclic AMP accumulation in rat parotid gland tissue.

The present study was carried out to determine the relationship of beta 1- and Beta 2-subtype to amylase release and cyclic AMP (cAMP) accumulation in rat parotid tissue. In in vitro experiments, beta-adrenergic agents (isoproterenol and dobutamine)-induced amylase release and cAMP accumulation were all completely inhibited by the beta 1-antagonist metoprolol, but incompletely inhibited by the beta 2-antagonist butoxamine. The beta 2-agonist procaterol caused little or no amylase release or cAMP accumulation. Our results suggest that both amylase release and cAMP accumulation in rat parotid tissue may be selectively induced by beta 1-adrenergic stimulation.

Adrenergic beta-Agonists↗
PubMed1985

Isoproterenol inhibition of potassium release from rat parotid gland.

The mechanism of isoproterenol-induced inhibition of potassium release from rat parotid slices has been determined. Spontaneous potassium release from the slices was significantly inhibited by isoproterenol at concentrations above 10(-6) M. This isoproterenol effect was completely abolished in the presence of propranolol (10(-5) M) and ouabain (10(-3) M) and was abolished during Na+-exclusion from the incubation medium. Isoproterenol caused an enhancement of the microsomal Na+, K+-ATPase activity at concentrations above 10(-5) M, and this activity was inhibited by propranolol (10(-5) M). The stimulatory effect of isoproterenol on the Na+, K+-ATPase exhibited a strong correlation with the inhibition of potassium release on each dose of isoproterenol. Moreover, dibutyryl cyclic AMP at concentrations above 10(-4) M inhibited potassium release in a dose-dependent manner and cyclic AMP caused an enhancement of the microsomal Na+, K+-ATPase activity. These results suggest that the inhibitory effect of isoproterenol on potassium release is clearly derived from the elevated Na+, K+-ATPase activity and that it may in part be mediated by cyclic AMP.

Animals↗
PubMed1985

Hypertrophy and dysfunction of parotid gland induced by chronic stimulation of beta 1-adrenergic receptors.

The present study was carried out to determine the beta-receptor subtype responsible for the hypertrophy and dysfunction of parotid glands in rats chronically treated with isoproterenol (ISP). Treatment with dobutamine (DBT), a beta 1-agonist, (30 mg/kg twice a day for 4 days) produced a significant enlargement of the parotid gland just as in the ISP-treated rats. The effects of secretagogues on amylase release and ISP-induced cyclic AMP accumulation were markedly decreased in the parotid tissue of the treated rats. Co-administration of the beta 1-antagonists metoprolol and acebutolol clearly inhibited the development of parotid enlargement and its secretory dysfunction induced by ISP or DBT. Procaterol treatment (30 mg/kg, twice a day for 4 days) did not cause any dysfunction or any increase in the gland weights. These results indicate that both hypertrophy and dysfunction of the rat parotid gland, which were observed in chronic treatment with ISP, may result from chronic stimulation of beta 1-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1984

Effects of repeated exposure to isoproterenol in vivo and in vitro on amylase release from rat parotid tissue.

Effects of repeated exposure to isoproterenol (ISO), in vivo and in vitro, were investigated on amylase release from rat parotid slices responding to secretagogues. Responses to ISO and dibutyryl cyclic AMP (DBcAMP) were reduced in the tissue from ISO-treated rats (3 mg/kg, 3 times daily for 3 days), but not in the tissue from propranolol plus ISO-treated rats. Administration of inhibitors of protein synthesis with ISO resulted in a protective effect with regard to development of decreased responses to ISO, DBcAMP and carbachol. A decreased response to ISO (10(-5) M) was caused by repeated exposure to ISO in vitro and could not be prevented by pretreatment with inhibitors of protein synthesis. Although the basal level of cyclic AMP in parotid tissue was lower in ISO-pretreated rats than in control rats, after incubation with ISO, the level of cyclic AMP did not differ between ISO-pretreated and control rats. These results suggest that the decreased response (amylase release) to ISO in the parotid tissue from ISO-pretreated rats may have been due to an impairment of common secretory process(es) involving various secretagogues and that the development of the impairment may be closely connected to the de novo synthesis of proteins induced by ISO, but not the impairment of the beta-adrenoceptor-adenylate cyclase system.

Amylases↗