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H Sasamura

Publications and source records attributed to H Sasamura.

29 records · Page 2Linked to original sources

Desensitization of angiotensin receptor function.

Angiotensin II is an eight amino acid peptide which plays a major role in the regulation of cardiovascular homeostasis. The physiologic effects of angiotensin (Ang) II are mediated by a G-protein coupled receptor, termed AT1, which activates phospholipase C. A major factor regulating angiotensin II receptor function is the rapid desensitization following agonist stimulation. However, despite years of investigation, the mechanism by which the angiotensin receptor is regulated remains unclear. The cloning of the AT-1 receptor and the availability of cell lines which stabily express this receptor has helped elucidate these mechanisms. In this paper, we review the data from our laboratory concerning the post-translational regulation of the angiotensin receptor function.

Animals↗

Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors.

Angiotensin II acts on at least two distinct receptor subtypes (AT1 and AT2). Most known effects of angiotensin II in adult tissues are attributable to the AT1 receptor. The function of AT2 receptor is undefined, but its abundant expressions in fetal tissues, immature brain, skin wound, and atretic ovarian follicles suggest a role in growth and development. Previous studies suggested that AT2 receptor may not be G protein-coupled. Here, from a rat fetus expression library, we cloned a cDNA encoding a unique 363-amino acid protein with pharmacological specificity, tissue distribution, and developmental pattern of the AT2 receptor. It is 34% identical in sequence to the AT1 receptor, sharing a seven-transmembrane domain topology. A review of prior data on other receptors suggests that this receptor may belong to a unique class of seven-transmembrane receptors (including somatostatin SSTR1, dopamine D3, and frizzled protein Fz) for which G protein coupling has not been demonstrated. All members of this class exhibit fetal and developmental and/or neuronal-specific expression. A conserved motif in the third intracellular loop, distinguishing this class from "classical" G protein-coupled receptors, may mediate novel intracellular effects.

Amino Acid Sequence↗

[A case report of pseudolymphoma of the kidney and orbit].

Pseudolymphoma is reactive extranodal lymphocytosis, and it's lymphocytes are so minimally atypical that it is basically benign. The patient was a 68-year-old female with pain in the left back and lower abdomen. Plain CT (computerized tomogram) of the kidney revealed a mass in the left kidney. It had a smooth surface and higher density than parenchyma. Similarly a left orbital mass was revealed by CT. We could not deny the mass to be a malignant tumor, so we took specimens from these lesions by an open biopsy. Histological examination of these specimens showed pseudolymphoma. Pseudolymphoma of the left kidney was reduced in its size by treatment with prednisolone. The patient is continuously followed up to date.

Aged↗

Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications.

AIM: To examine the nature of multiple putative enzymatic pathways, review the evidence of angiotensin receptor heterogeneity and speculate on the implications for physiology and pharmacology. METHOD: Literature review and discussion of current research. RESULTS: New information on the renin-angiotensin system suggests that the pathways of angiotensin production are complex and that multiple receptor subtypes mediate angiotensin actions. CONCLUSIONS: The differences in structure and tissue distribution of different subtypes of angiotensin receptor may explain differences in receptor regulation in various tissues. The type 2 receptor may be primarily an embryonic receptor involved with cell differentiation and growth and may be induced in disease states. The existence of angiotensin receptor subtypes provides an opportunity for the development of receptor-specific antagonists.

Amino Acid Sequence↗

Cloning, characterization, and expression of two angiotensin receptor (AT-1) isoforms from the mouse genome.

We report the existence of two structurally distinct forms of the angiotensin receptor AT-1 in the mouse. A Balb/c mouse genomic library was screened by homology screening with a polymerase chain reaction (PCR) amplified probe. Restriction mapping and sequencing of the isolated genes revealed the presence of two receptor isoforms, here named the mouse AT-1a and AT-1b receptors, containing 22 different amino acids. Receptor binding studies performed on COS-7 cells transfected with the two receptors revealed that they had similar binding profiles for angiotensin II, angiotensin III and AT-1 or AT-2 specific antagonists. Because many of the structural differences were in the carboxy terminal putative intracellular domain, we speculate that these isoforms may differ in their regulation, signal transduction, or desensitization mechanisms.

Amino Acid Sequence↗

Repeated intestinal ulcerations in a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels.

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

Adult↗

Effect of growth hormone on rat hepatic cytochrome P-450f mRNA: a new mode of regulation.

Growth hormone (GH) is known to be involved in the control of rat hepatic drug and steroid metabolism through its action on cytochrome P-450s. To examine the role of GH in the regulation of cytochrome P-450f (P-450f), a full-length cDNA clone corresponding to P-450f was isolated and the 3'-non-coding region was utilized for Northern and slot-blot analyses. P-450f mRNA levels were low in neonates, increased after age 4 weeks in male and female rats, and were approximately 3 times higher in the liver of adult female rats than male rats. Hypophysectomy caused a significant decrease in P-450f mRNA levels in male and female rats. Intermittent injection with human growth hormone (hGH) to mimic the male secretory pattern of GH caused a 9-fold increase in P-450f mRNA in hypophysectomized male rats to levels near male control levels, whereas continuous administration of hGH to mimic the female secretory pattern caused a greater increase in P-450f mRNA levels in male and female hypophysectomized rats (25-fold and 9-fold respectively) to levels nearer female control levels. The responses of the other GH-stimulated P-450s, P-450-male and P-450-female, to the different modes of hGH treatment were different from that of P-450f. Since sex hormones are known to affect the regulation of other P-450s, the effect of sex hormones on P-450f mRNA was studied. Ovariectomy caused a 2.4-fold reduction in P-450f mRNA which was partially reversed by estradiol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of angiotensin II, ACTH, and KCl on the adrenal renin-angiotensin system in the rat.

Angiotensin II, ACTH and potassium chloride were administered to rats for 6 days and the effects on adrenal renin-like activity and adrenal angiotensin II/III immunoreactivity were investigated. Rats infused with angiotensin II (140 pmol/min) either ip or sc showed increases in adrenal angiotensin II/III immunoreactivity (p less than 0.05) and plasma aldosterone concentration (p less than 0.05), but no change in adrenal renin-like activity. Captopril treatment of angiotensin II-infused rats caused a slight decrease in angiotensin II/III immunoreactivity which did not reach statistical significance. In contrast, rats treated with ACTH (Cortrosyn-Z, 3 IU/day, sc) showed an increase in adrenal renin-like activity (p less than 0.01), but no significant change in adrenal angiotensin II/III immunoreactivity. Rats treated with KCl in drinking water showed increases (p less than 0.05) in adrenal renin-like activity, adrenal angiotensin II/III immunoreactivity, and plasma aldosterone. These results suggest that angiotensin II, ACTH and potassium, three major regulators of aldosterone secretion by the adrenal gland, have different effects on the adrenal renin-angiotensin system when administered in vivo.

Adrenal Glands↗

Response of plasma immunoreactive active renin, inactive renin, plasma renin activity, and aldosterone to hemodialysis in patients with diabetic nephropathy.

Several alterations in plasma active renin, inactive renin (prorenin), and aldosterone have been described in patients with diabetes mellitus. Such changes could be of some importance for patients on hemodialysis treatment, who must undergo severe changes in fluid and electrolyte status during each dialysis session. Therefore we studied the response of renin and aldosterone to hemodialysis in uremic diabetic nephropathy patients, using direct immunometric assays to measure plasma active renin concentration (ARC), inactive renin concentration (IRC), total renin concentration (TRC), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) in 11 male patients aged 39-69 (mean 53 +/- 2) with diabetic nephropathy and 11 male age-matched non-diabetics who had been on maintenance hemodialysis for 1-10 years. Although baseline values of IRC were slightly higher, and values of PAC lower in diabetics compared to non-diabetics, the results did not reach statistical significance. During hemodialysis, significant increases in ARC (p less than 0.01), TRC (p less than 0.05), and PRA (p less than 0.01), and a significant decrease (p less than 0.05) in PAC were seen in non-diabetic patients but no significant changes were observed in patients with diabetic nephropathy. IRC did not change during hemodialysis in either group of patients. There were no significant differences in body weight, blood pressure, or electrolyte changes in the two groups. These results suggest an altered response of plasma renin and aldosterone to hemodialysis in patients with diabetic nephropathy compared to non-diabetics. The reduced renin response could not be explained by a defect in conversion from inactive renin, but may be caused by decreased secretion of active renin in these patients.

Adult↗