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Biomedical subjects

S Hatta

Publications and source records attributed to S Hatta.

At least 55 records · Page 3Linked to original sources
PubMed1994

Alterations of receptor-G protein-adenylyl cyclase coupling in alcoholics.

This study investigated alterations in the receptor adenylyl cyclase system in the brain and platelets of alcoholics through the study of GTP binding (G) protein, which has a key role in the system, in the membranes of the post-mortem brain and platelets. Quantitative examination of G protein by immunoblotting showed that GsH alpha in the temporal cortex of the post-mortem alcoholic brain was significantly decreased with controls. Moreover, the extent of ethanol enhancement of functional photoaffinity GTP(azidoanilido GTP) labeling to Gs alpha and Gi alpha was decreased in all cortical regions (frontal, temporal, parietal, occipital cortex) from alcoholics. In the platelet membrane, a quantitative reduction in GsH alpha and GsL alpha levels as assessed by immunoblotting was seen in family history positive (FHP) alcoholics. A reduction in ethanol enhancement of AAGTP labeling to Gs alpha and Gi alpha was also observed in the FHP group. These alterations of G protein were not found in the platelets from family history negative (FHN) alcoholics. The dysfunctions of Gs protein occurring in platelet membranes of the FHP group are likely to parallel those that occur in the alcoholic brain. These results suggest that disturbances of G protein-mediated signal transduction may be involved in the pathophysiology of alcoholics and that platelet G protein may be used as a trait marker of alcoholics.

Adenylyl Cyclases↗
PubMed1994

Effects of ethanol on the function of G proteins in rat cerebral cortex membranes.

The acute effects of ethanol on the function of G protein in rat cerebral cortical membranes were examined using immunoblotting and photosensitive GTP labeling. Ethanol potentiated GppNHp-dependent activation of adenylyl cyclase and inhibition of forskolin-stimulated activity of the enzyme in corticol membranes from Wistar rats. It also enhanced guanine nucleotide binding to Gs and Gi as estimated by photoaffinity labeling. However, ethanol had no effects on the contents of Gs/alpha, Gi(1) alpha and Gi(2) alpha, and G beta subunits. While it potentiated Gi-mediated inhibition of adenylyl cyclase in Wistar rats, ethanol had no effect on the inhibitory regulation of the enzyme in the membranes from Fischer 344 rats. These results suggest that ethanol in vitro enhances both Gs and Gi functions in cerebral cortical membranes from Wistar rats and that the Gi function in the cerebral cortex may be differentially regulated by ethanol in Wistar and Fischer 344 rats.

Adenylyl Cyclases↗
PubMed1994

Reduced sensitivity to ethanol of Gs alpha and Gi/o alpha in the cerebral cortex of alcoholic patients.

In this study, we examined the quantity and quality of G proteins in membrane preparations from cortical regions (frontal, parietal, temporal and occipital cortex) in post-mortem brains obtained from subjects with chronic alcoholism and controls matched with respect to age and post-mortem delay (PMDT). Immunoblot analysis showed that the level of GsH alpha (52 kDa) was significantly decreased in temporal cortical membranes from alcoholics compared with controls, while no differences were observed in the amount of any G protein in frontal, parietal and occipital regions. Additionally, ethanol enhanced photoaffinity guanine nucleotide binding to both G alpha and Gi/o alpha in human cortical membranes. The percentage of increase in ethanol-stimulated photoaffinity GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholic patients in all cortical regions. These observations indicated that subsensitivities to ethanol-induced stimulation in G protein may contribute to impaired trans-signaling in cortical membranes of chronic alcoholics.

Alcoholism↗
PubMed1993

Alterations of guanine nucleotide-binding proteins in post-mortem human brain in alcoholics.

Qualitative and quantitative alterations of G proteins in membrane preparations from parietal and temporal cortex regions in post-mortem brains obtained from alcoholics and controls matched with respect to age and post-mortem delay were investigated by Western-blotting with polyclonal antibodies against specific G protein subunits and functional photoaffinity GTP binding. Quantitative immunoblotting showed that only Gs alpha (52 kDa species) in temporal cortex was significantly decreased (30%, P < 0.05) in alcoholics compared with controls. Moreover, ethanol-stimulated photoaffinity GTP labeling of Gs alpha and Gi/o alpha was decreased in alcoholics in both cortex regions. These results suggest that disturbances of G protein-mediated signal transduction may be involved in the pathophysiology of alcoholics.

Aged↗
PubMed1993

Effects of ceruletide on the dopamine receptor-adenylate cyclase system in striatum and frontal cortex of rats chronically treated with haloperidol.

Chronic treatment of rats with haloperidol decanoate (30 mg/kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [3H] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [3H] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 micrograms/kg IP twice a day for 5 days). [3H] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [3H] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [3H] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 microM or 100 microM) or Gpp(NH)p (1 microM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1993

Relation of blood pressure circadian rhythm to cardiovascular complaints and orthostatic test results in patients with orthostatic dysregulation. Effects of midodrine on blood pressure circadian rhythm.

Twenty patients with orthostatic dysregulation were studied in order to clarify the relation of blood pressure (BP) circadian rhythm to cardiovascular complaints and orthostatic test results. There was a significant negative correlation between the number of cardiovascular complaints and 24 hour (hr) maximum (Mx) and day-time Mx BPd. A significant negative correlation was also obtained between the decrease in TII amplitude in upright posture and nighttime standard deviation and range of BPs and BPd. Decrease of BPs in upright posture was significantly correlated with 24 hr and nighttime minimum (Mn) BPd. The above results indicate that cardiovascular complaints and orthostatic test results are related with BPd, as well as BPs.

Blood Pressure↗
PubMed1993

[Effects of ethanol on Gi protein function in rat cerebral cortex of Wistar and Fischer 344 rats: evaluation by low pH treatment].

The present study was designed to provide further information regarding the effect of ethanol on the function of inhibitory GTP-binding (Gi) protein. To eliminate the Gs function in the regulation of adenylyl cyclase, cerebral cortex membranes from Wistar or Fischer 344 rats were pretreated at pH 4.5 ("low pH"), whereupon Gpp(NH)p-dependent inhibition of forskolin-stimulated adenylyl cyclase was examined. In the membranes from Wistar rats, ethanol (100 or 250 mM) resulted in left-shifted Gpp(NH)p inhibition curves and reduced IC50 values for Gpp(NH)p in an ethanol dose-dependent manner. In contrast, ethanol exhibited no effect on the Gpp(NH)p-dependent inhibition of the enzyme or on IC50 values for Gpp(NH)p in the membranes from Fischer 344 rats. These results are consistent with the idea that ethanol, in vitro, enhances the Gi function in the cerebral cortex of Wistar rats, and that ethanol's effect on Gi protein in the cerebral cortex is different in Wistar and Fischer 344 rats.

Animals↗
PubMed1993

[Effects of ethanol on GTP-binding protein function in human brain cortex].

The effect of ethanol "in vitro" on GTP-binding protein in postmortem human brain cortex membranes was analyzed using by photoaffinity hydrolysis resistant GTP analog (azidoanilido GTP, AAGTP). AAGTP identified stimulatory GTP binding protein [Gs alpha (42 KDa)] and inhibitory GTP binding protein [Gi alpha (40 KDa)] in human brain cortex membranes. Ethanol augmented the amount of AAGTP binding to both Gs alpha and Gi alpha in human temporal and parietal cortex membranes. These results show that ethanol "in vitro" elevates not only Gs functions but also Gi functions in postmortem human brain cortex.

Aged↗
PubMed1993

[A 70-year-old man with right hemiparesis and mutism].

We report a 70-year-old man who had a sudden onset of right hemiparesis and mutism. The lower extremity was more involved than the upper one. He had a long history of diabetes and chronic renal failure for which hemodialysis was necessary. On August 30, 1990, he had an sudden onset of right hemiparesis and mutism. Neurological examination revealed awake but mute in no acute distress. He could only respond to very simple commands such as opening his mouth or protruding his tongue. He did not appear to understand more difficult questions. In addition, he could not answer verbally. He was totally mute. Cranial nerves appeared intact except for slight right central facial paresis and severe diabetic retinopathy. He had complete paralysis of his right leg and a moderate weakness in his right upper extremity. Deep reflexes were diminished in both upper extremities and absent in the lower limbs. Frotal signs such as grasp and snout reflexes were present. Cranial CT scans revealed an ill-defined low density area in the left parasagittal subcortical area and a part of the anterior cerebral artery territory. The supplementary motor area appeared at least in part to be involved. He was treated with glycerol and other supportive cares, however, his clinical course was complicated by pneumonia, heart failure, septicemia, and he expired two months after his stroke. The patient was discussed in a neurological CPC, and the chief discussant arrived at a conclusion that he had an artery-to-artery embolism at the internal carotid bifurcation resulting in the cerebral infarction mainly in the territory of the anterior cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Effects of intraocular pressure on the optic nerve head in albino rabbits].

The effects of intraocular pressure (IOP) on the blood flow in the laminar portion of the optic nerve head in adult albino rabbits were investigated employing the hydrogen clearance method. The blood flow volume at the normal IOP level of 15 mmHg was 119.0 +/- 25.0 ml/min/100 g (mean +/- S.D.). When the IOP was raised every 30 minutes from 5 mmHg to 15, 25, 35, 45 and 55 mmHg in a stepwise fashion, the mean blood flow volume at 5 mmHg was almost the same as the volume at 15 mmHg, but a significant linear decrease was observed at 35 mmHg or more. The decreased blood flow returned to the initial level when the raised IOP was restored to normal. When the IOP was raised to 55 mmHg, the optic nerve potential (ONP) amplitude decreased and the peak latency became gradually prolonged with time, and finally the ONP became almost impossible to measure after 30 minutes, before remarkable changes were noted on the electroretinogram. However, quick recovery of the ONP was recognized within 5 minutes after returning to a normal IOP level of 15 mmHg. These findings indicate that vascular changes might have an important effect on the optic nerve head function or action potential.

Animals↗
PubMed1991

Enhancement in beta-adrenergic responsiveness of adenylate cyclase in rat liver after galactosamine administration.

In rat liver at 48 hours after galactosamine (GalN) treatment, isoproterenol-induced accumulation of cyclic AMP and activation of adenylate cyclase (AC) were significantly enhanced. AC activity stimulated with GppNHp or NaF was also augmented in membranes from GalN-treated rats. However, the MnCl2-stimulated or forskolin-stimulated activity in GalN-treated rats did not differ from the control. These data suggest that the beta-adrenergic responsiveness of AC in rat liver is potentiated, possibly due to the enhanced function of the Gs protein, during the process of regeneration after GalN treatment.

Adenylyl Cyclases↗
PubMed1991

Stable inhibition of adenylate cyclase by muscarinic agonist in rat parotid gland: effects of neomycin and pertussis toxin.

Treatment of rat parotid slices with carbachol (CCh) resulted in the stable inhibition of isoproterenol-induced activation of adenylate cyclase (AC); the inhibition of the enzyme was persistently observed in washed membrane prepared from parotid slices pretreated with CCh. Methoxamine, but not clonidine, also caused stable inhibition. Activation of AC by 5'-guanylylimidodiphosphate (GppNHp) and by NaF was also attenuated by treatment with either CCh or methoxamine, indicating reduction of the Gs protein function. Pertussis toxin treatment prevented CCh-induced inhibition of the enzyme. However, MnCl2-stimulated and forskolin-stimulated activity, and the inhibition of forskolin-stimulated activity by GppNHp were not altered by CCh treatment. It appears, therefore, that the stable muscarinic inhibition of AC involves the Gi protein, but it does not result from the inhibitory regulation of AC activity by the interaction between the Gi protein and the catalytic unit of AC. Furthermore, the inhibition of GppNHp-stimulated AC activity by CCh was effectively reversed by the pretreatment of slices with neomycin. This suggests that the stimulation of phosphoinositide hydrolysis elicited by CCh possibly participates in stable muscarinic inhibition of AC presumably by reducing the function of the Gs protein. Thus, in the rat parotid gland, CCh appears to cause a stable inhibition of AC through two different mechanisms; one is associated with the Gi protein and the other is associated with the stimulation of phosphoinositide metabolism.

Adenylate Cyclase Toxin↗
PubMed1990

In situ detection of cutaneous melanoma by prompt gamma-ray spectrometry using melanoma-seeking 10B-dopa analogue.

10B1-para-boronophenylalanine (10B1-BPA), one of our boronated dopa analogues developed for thermal neutron capture therapy, has been found to have a selective affinity for malignant melanoma. We have established a method of 'in situ' detection of subcutaneous melanoma lesions, using this melanoma-seeking 10B-labeled compound. In this study, we applied an 'in situ' 10B microanalysis system via detection of the prompt gamma-ray from the 10B(n, alpha)7Li reaction triggered by irradiating the 10B-containing target with pure thermal neutrons, called prompt gamma-ray spectrometry, to hamsters bearing Greene's melanoma in subcutis and to a human patient whose occipital subcutaneous tumor was suspected of being a metastatic melanoma. In the hamsters, the time-dependent 10B dynamics showed increased 10B accumulation in melanoma, after 10B1-BPA administration, in contrast to that in non-melanoma normal skin. In the human patient, after subcutaneous injection of 10B1-BPA into perilesional sites 4 cm distant from the tumor margin, the average 10B concentration in the tumor was determined to be 24 ppm (microgram/g), in contrast to 3 ppm in skin covering the tumor and 1.1 ppm in blood, indicative of selectively high 10B1-BPA uptake by the tumor.

Aged↗
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 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↗