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Biomedical subjects

K Urasawa

Publications and source records attributed to K Urasawa.

32 records · Page 2Linked to original sources
PubMed1992

Endothelin inhibits adenylate cyclase and stimulates phosphoinositide hydrolysis in adult cardiac myocytes.

We have assessed the effects of endothelin-1 (ET-1) on transmembrane signaling in adult rat ventricular myocytes. ET-1 stimulates phosphoinositide hydrolysis with an EC50 of 0.3-0.8 nM. This stimulation is linear for up to 30 min in the presence of a protease inhibitor, is additive with the effects of other stimulators of phosphoinositide hydrolysis, is not inhibited by the Ca2+ entry blocker, nifedipine, and is insensitive to pertussis toxin. ET-1 also reduces cyclic AMP production in myocytes in response to isoproterenol and forskolin (EC50, 1 nM). This cyclic AMP-lowering effect of ET-1 is sensitive to pertussis toxin, can be demonstrated directly in assays of adenylate cyclase activity of myocyte membranes, and seems to be mediated by Gi. These data indicate that the effects of endothelin on adult cardiac myocytes involve multiple signaling pathways, including enhanced activity of the inositol phosphate pathway and a decrease in cyclic AMP-mediated responses, neither of which seems likely to account for the positive contractile effects of endothelin.

Adenosine Diphosphate Ribose↗
PubMed1992

A substantial proportion of cardiac Gs is not associated with the plasma membrane.

The precise interactions between the subunits of Gs (alpha s, beta, gamma) and the plasma membrane remain to be established. If alpha s is associated loosely with the inner membrane, is labile during activation, or is always present to some extent in the cytoplasm, then it should fractionate to the supernatant of a high-speed centrifugation. We identified abundant alpha s (52-66% of total cellular) in the supernatant fraction of right atrial and left ventricular membrane preparations of porcine heart as shown by two distinct measures of alpha s (immunoblotting and ADP ribosylation by cholera toxin). However, functional assays utilizing reconstitution of cardiac alpha s with cyc- S49 membranes revealed that the supernatant fraction contained approximately 16% of total cellular alpha s activity. The alpha s present in the supernatant fraction did not result from contamination by sarcolemmal membrane fragments. We conclude that traditional methods for quantifying alpha s which utilize only detergent extracts from high-speed pellets do not account for a sizable proportion of total cellular alpha s, but that the majority of this population of cardiac alpha s may not be functional, at least with respect to adenylyl cyclase activation.

Adenosine Diphosphate Ribose↗
PubMed1992

A mechanism of catecholamine tolerance in congestive heart failure--alterations in the hormone sensitive adenylyl cyclase system of the heart.

It is well known that failing hearts show diminished responsiveness (desensitization) to catecholamines. In this study, 2 different animal models were used to investigate the alterations in the hormone sensitive cardiac adenylyl cyclase system in a congestive heart failure. In the first model, cardiomyopathic Syrian hamsters (BIO53.58), we found reduced activity of the catalytic protein of adenylyl cyclase; this reduction was more prominent in an older animals (28-week-old vs 16-week-old). At both ages, the amount of inhibitory GTP-binding protein (Gi) was markedly increased in BIO53.58 compared to control healthy hamsters. Moreover the increased Gi was shown to be fully functional in the inhibitory pathway of the adenylyl cyclase system. In the second model, chronically norepinephrine-infused rats, we found a decrease in beta-adrenergic receptor density at an early stage of injection (3 days), while the activity of catalytic protein decreased beyond 14 days of injection, and the amount of Gi increased after 7 days of injection. These results suggest that increased plasma catecholamine concentrations in the setting of congestive heart failure might be a major trigger for qualitative and quantitative alterations observed in various components of cardiac adenylyl cyclase system, and that GTP-binding proteins and catalytic protein of adenylyl cyclase are involved in the mechanism of desensitization especially after chronic in vivo stimulation of adrenergic receptors.

Adenylyl Cyclases↗
PubMed1992

[Immunological functions and clinical course of elderly patients with cerebrovascular diseases].

In the elderly, cerebrovascular diseases (CVD) are often complicated by severe infections such as pneumonia. This study aimed to examine the possible relationship at various timepoints of observation between immunological functions and the clinical course and to correlate the changes of immunological functions with CVD lesion side. The study was based on 25 right-handed patients (14 male and 11 female, mean age; male 69.0 years and female 74.9 years) with acute, focal neurological deficits of CVD (5 cerebral bleeding, 20 cerebral infarction; 11 right cerebral lesioned subjects, 14 left cerebral lesioned subjects). All patients were evaluated in terms of lymphocyte counts, T, B cell counts, T cell subsets, lymphocyte transformation and natural killer activity in peripheral blood as indices of immunological functions at various timepoints during the clinical course. Some of these immunological functions decreased within two months (acute stage) after onset of CVD, and some cases with decreased immunological functions developed complications of severe infection such as pneumonia. Patients who had both decreased immunological function and severe infection were 1 out of cases with 7 right cerebral lesions and 6 out of with 9 left cerebral lesions. This study suggests that the decreased immunological function in CVD subjects may be correlated with the site of the CVD lesion. In all left cerebral lesioned subjects, a reduction of immunological functions and a susceptibility to severe infection were not observed in the acute stage of CVD, however, some left cerebral lesion cases may be more closely related than in right cerebral lesion cases. The mechanism remains to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Age-related alterations in adenylyl cyclase system of rat hearts.

Cardiac membranes from 26-, 52- and 104-week-old Wistar rats were used to investigate the age-related alterations in the beta-adrenergic receptor-adenylyl cyclase system. The densities and affinities of beta-adrenoceptors did not change with aging. There were no significant changes in the total amount of stimulatory G-protein (Gs), and in Gs activity measured in a reconstitution assay using human platelet membranes. The major isoform of Gs alpha, however, changed from a 45,000 to 52,000 dalton peptide with aging. The total amount of pertussis toxin substrates (Gi2 and Go) decreased significantly with aging. This finding was supported by the fact that pertussis toxin-induced potentiation of adenylyl cyclase activity was markedly reduced in the aged group. The activity of catalytic protein assessed by forskolin-stimulated adenylyl cyclase activity was decreased at 104 weeks. On the other hand, GTP analogue-stimulated adenylyl cyclase activity was significantly potentiated in the same group. These results suggest that the decreased sensitivity to catecholamines observed in aged hearts is mainly due to a dysfunction of catalytic protein, and that decreased Gi activity partially compensates for this catalytic dysfunction.

Adenosine Diphosphate↗
PubMed1990

Purification of pertussis toxin substrates from bovine heart membranes.

Pertussis toxin substrates were purified from bovine heart membranes by means of a sequential column chromatographic techniques. The elution pattern from the final ion-exchange chromatography and relative mobilities of these peptides on SDS-polyacrylamide gel electrophoresis revealed that the bovine heart membranes contained two distinct pertussis toxin substrates: Gi2 and Go.

Adenylyl Cyclase Inhibitors↗
PubMed1987

[Development- and age-related alterations of beta-adrenergic receptor--adenylate cyclase system in rat myocardium].

It is well known that myocardial responsiveness to catecholamines declines with age besides the elevation of plasma catecholamine concentration. Moreover, age-related alterations in beta-adrenergic receptor-adenylate cyclase system are thought to be a mechanism of the decreased responsiveness. In this study, using Wistar rat myocardium (3, 26, 52, 104 weeks old), alterations in beta-adrenergic receptor (Rs), stimulatory guanine nucleotide-binding protein (Gs), inhibitory guanine nucleotide-binding protein (Gi), and catalytic unit of adenylate cyclase system (C) were investigated. All components consisting the system altered with development and aging: 1) The density of Rs (Bmax) decreased with development. On the other hand, the dissociation constant of Rs (Kd) to Iodocyanopindolol did not change. 2) Forskolin-stimulated activity of C decreased significantly between 3 and 26, between 52 and 104 weeks old. 3) Activity of Gs decreased with development, and did not with aging. In addition, SDS-PAGE and autoradiography revealed that the major alpha-subunits of Gs ADP-ribosylated by cholera toxin changed from peptides of Mr = 45,000 and 47,000 to peptide of Mr = 52,000 with aging. 4) The function of G1 declined with aging. And it was confirmed in this study that function of G1 declined with aging. And it was confirmed in this study that alpha-subunit of Gi ADP -ribosylated by IAP (islet-activating protein) decreased with development and aging.

Adenylyl Cyclases↗
PubMed1986

[Analysis of ventricular wall motion using multislice ECG-gated cardiac X-ray CT: application of the three-dimensional reconstruction technique].

A new computer system was proposed to evaluate abnormal motion of the ventricular wall in patients with myocardial infarction. Multi-slice ECG-gated cardiac X-ray CT (MSECT), a new technique developed in our laboratory, was the source of the original image. Using this system, we reconstructed three-dimensional images, calculated % shortening values of the entire heart, and visualized abnormal wall motion on the ventricular surface, displaying three-dimensionally. Our initial study of five patients with myocardial infarction showed good correlation between the findings using this system and conventional echocardiography and cine-ventriculography. Since the development of the ECG-gated method, the application of CT to the study of heart diseases has progressed rapidly. In patients with myocardial infarction, ECG-gated cardiac CT is used to visualize infarcted myocardium and to evaluate impaired cardiac function. However, such analyses were limited to single slices, because a large dose of contrast medium was required to distinguish the ventricular chamber from the myocardium. By adopting multi-slice ECG-gated cardiac X-ray CT images as the data source and using three-dimensional reconstruction technique, this system is useful for evaluating abnormal wall motion.

Adult↗