Biomedical subjects

M Mukoyama

Publications and source records attributed to M Mukoyama.

At least 19 recordsLinked to original sources

PubMed1996

Demonstration of slow acetylator genotype of N-acetyltransferase in isoniazid neuropathy using an archival hematoxylin and eosin section of a sural nerve biopsy specimen.

The genotype for N-acetyltransferase was analyzed in five Japanese patients with isoniazid neuropathy by using the allele specific polymerase chain reaction for a single slice of the 30-year-old paraffin-embedded and hematoxylin-eosin stained sural nerve biopsy specimens. We found slow acetylator genotypes for N-acetyltransferase in all isoniazid neuropathy patients. This result confirmed that patients with the slow acetylator genotype tend to develop neuropathy after administration of isoniazid.

Acetylation↗

PubMed1996

The natriuretic peptide family.

The natriuretic peptide system is a complicated system comprising at least three endogenous peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide) and three receptors [the atrial natriuretic peptide-A receptor (guanylyl cyclase A), the atrial natriuretic peptide-B receptor (guanylyl cyclase B) and the clearance receptor]. The accumulated evidence indicates that this system is implicated in the control of blood pressure, body fluid homeostasis and vascular remodelling as cardiac hormone and local regulator.

Animals↗

PubMed1996

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Sar1, Ile5]Ang II, most (> 90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), Bmax for the AT2 receptor was significantly decreased (62 +/- 17 and 25 +/- 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 Bmax (54 +/- 12 fmol/mg protein, n = 4). AT2 Bmax or Kd values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant. AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

Adult↗

PubMed1996

C-type natriuretic peptide in chronic renal failure and its action in humans.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.

Adult↗

PubMed1995

The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2.

Angiotensin II type 2 (AT2) receptor is abundantly and widely expressed in fetal tissues but present only in restricted tissues in the adult such as brain and atretic ovary. This receptor is speculated to be involved in tissue growth and/or differentiation. To elucidate the molecular mechanism of growth-regulated AT2 receptor expression, we cloned the mouse AT2 receptor genomic DNA and studied its promoter function in mouse fibroblast-derived R3T3 cells, which express AT2 receptor in the confluent, quiescent state but very low levels of the receptor in actively growing state. Promoter/luciferase reporter deletion analysis of AT2 receptor in R3T3 cells showed that the putative negative regulatory region is located between the positions -453 and -225, which plays an important role in the transcriptional control of AT2 receptor gene expression along with the cell growth. We identified the interferon regulatory factor (IRF) binding motif in this region using DNase foot-printing analysis and demonstrated that IRF binding oligonucleotide treatment increased the AT2 receptor expression in growing R3T3 cells but not in confluent cells. Furthermore, by antisense treatment, we demonstrated that IRF-2 attenuated the AT2 receptor expression in both growing and confluent R3T3 cells, whereas IRF-1 enhanced AT2 receptor expression in the confluent cells only. Consistent with this result, gel mobility shift assay demonstrated that growing R3T3 cells exhibited only IRF-2 binding, whereas confluent cells exhibited both IRF-1 and IRF-2 binding. Furthermore, we observed using reverse transcription-polymerase chain reaction that the IRF-1 mRNA expression was more abundant in confluent cells than growing cells, whereas IRF-2 expression did not change with R3T3 cell growth. We conclude that, in confluent cells, the enhanced expression of IRF-1 antagonizes the IRF-2 effect and increases the AT2 receptor expression. We speculate that these transcriptional factors influence cell growth in part by regulating AT2 receptor expression.

3T3 Cells↗

PubMed1995

Effects of cilostazol on development of experimental diabetic neuropathy: functional and structural studies, and Na+ -K+ -ATPase acidity in peripheral nerve in rats with streptozotocin-induced diabetes.

We studied the ability of cilostazol (CL), an antithrombotic and vasodilating agent, to prevent functional, structural and biochemical abnormalities including delayed motor nerve conduction velocity (MNCV), morphological changes in myelinated fibers, and decreased Na(+)-K(+) -ATPase activity in the peripheral nerves of rats with streptozotocin (STZ)-induced diabetes. Cilostazol treatment (30 mg/kg/day p.o.) for 10 weeks significantly prevented the delay in MNCV in the tail nerve, and morphometric analysis of the sural nerves revealed that this dose of cilostazol had a significant effect on reduction of average size of myelinated fibers. In untreated diabetic rats, cyclic AMP content and Na(+)-K(+)-ATPase activity of peripheral nerve were each significantly less than in normal control rats. Cilostazol (30 mg/kg/day) prevented reduction of Na(+)-K(+)-ATPase activity. Decrease in cyclic AMP content was completely prevented with both doses of cilostazol (30 and 10 mg/kg/day). These findings suggest that cilostazol may have beneficial effects in the treatment of diabetic neuropathy, possibly via improvement of nerve Na(+)-K(+) -ATPase activity and cyclic AMP content. Cilostazol may thus be a potent drug for the clinical treatment of diabetic neuropathy.

Animals↗

PubMed1995

Characterization of a rat type 2 angiotensin II receptor stably expressed in 293 cells.

A cDNA clone for the rat type 2 (AT2) angiotensin II receptor was stably transfected into human embryonic kidney 293 cells. Binding characteristics of CGP42112A (Kd = 0.18 nM, Bmax = 10.8 pmol/mg protein) and ligand specificity were indistinguishable from those obtained with the whole rat fetus and with transiently transfected COS-7 cells. Non-hydrolyzable guanine nucleotide analogs did not affect the ligand binding curve; interestingly, the guanine nucleotide analog's effect was observed in the presence of sulfhydryl reducing agent, suggesting that a certain redox condition may affect G protein coupling to this receptor. Using the established cell line, several second messenger systems were assessed. None of cAMP levels, cGMP levels, arachidonic acid release, or phosphotyrosine phosphatase activity was affected by angiotensin II stimulation of this receptor. Furthermore, the AT2 receptor did not undergo agonist-stimulated internalization. These results using the cloned receptor suggest that the transfected AT2 receptor fails to effectively couple to the major G protein-mediated signaling mechanisms and ligand-activated internalization in transfected 293 cells.

Angiotensin II↗

PubMed1995

Umbilical venous guanosine 3',5'-cyclic phosphate (cGMP) concentration increases in asphyxiated newborns.

Guanosine 3',5'-cyclic phosphate (cGMP) is known to be the second messenger of natriuretic peptides and nitric oxide (NO). To investigate the involvement of natriuretic peptides in the regulation of the feto-placental circulation, specific radioimmunoassays were used to measure the concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cGMP in the umbilical venous plasma of normal and asphyxiated newborns. The plasma concentrations of ANP, BNP and cGMP in asphyxiated newborns were 48.3 +/- 12.9 pm, 24.5 +/- 9.4 pm and 4.4 +/- 1.6 nM (mean +/- s.e.m., n = 10), respectively. These values were significantly higher than those in the normal newborns (17.4 +/- 1.9 pm, 4.7 +/- 1.0 pm, and 0.78 +/- 0.14 nM, respectively). Moreover, the expression of both ANP-A and ANP-B receptor, biologically active receptors for natriuretic peptides, was detected in term human placenta by Northern bolt analysis. The expression of natriuretic peptide receptors was further confirmed by binding assay using [125I]-labelled ANP and solubilized crude membrane preparations of placental tissue. These findings suggest that cGMP is produced in the placenta, at least partly, by the action of ANP and BNP secreted from fetal heart, in pathophysiological conditions such as fetal hypoxia.

Asphyxia Neonatorum↗

PubMed1995

Altered gene expression of natriuretic peptide receptor subtypes in the kidney of stroke-prone spontaneously hypertensive rats.

1. To elucidate the physiological and pathophysiological role of the natriuretic peptide system in the progression of hypertensive renal disease, we examined the gene expression of natriuretic peptide receptor subtypes, guanylate cyclase-A (GC-A), guanylate cyclase-B (GC-B) and clearance receptor (C receptor), in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP) at 8 and 20 weeks of age, and compared them with their gene expression in age-matched Wistar-Kyoto (WKY) rats. 2. Northern blot analyses revealed that messages for three natriuretic peptide receptor subtypes were expressed in the kidney, and their expressions were higher in the glomeruli than in the whole kidney in each strain. 3. In 20 week old rats with established hypertension, the glomerular concentration of GC-A mRNA was significantly higher in SHRSP than in WKY. The concentrations of GC-B and C receptor mRNA in the glomeruli tended to increase and decrease, respectively, but they were not statistically significant in SHRSP. 4. In 8 week old rats, the glomerular concentrations of GC-A, GC-B and C receptor mRNA were not significantly different between SHRSP and WKY. 5. This study demonstrates that in the progression of hypertension, the expression of GC-A, which mediates biological actions of natriuretic peptides, is enhanced in the kidney of SHRSP compared to that of WKY. Together with the augmented secretion of the ligands previously revealed, altered expression of natriuretic peptide receptor subtypes in SHRSP may have a deterrent role in the development of hypertension and its renal complications.

Animals↗

PubMed1995

Preparation of a monoclonal antibody against mouse brain natriuretic peptide (BNP) and tissue distribution of BNP in mice.

1. In order to explore the significance of brain natriuretic peptide (BNP), a cardiac hormone secreted from the ventricle, in mice, we prepared a monoclonal antibody against mouse BNP (mBNP) and established a specific radioimmunoassay (RIA) for mBNP. 2. A monoclonal antibody, KY-mBNP-I, was prepared by the fusion of mouse myeloma cells X63-Ag8.653 with spleen cells of the BALB/c mouse immunized with synthetic mBNP[108-121] conjugated to bovine thyroglobulin. KY-mBNP-I belonged to an IgG2a subclass and showed a high affinity for mBNP (Ka = 1.8 x 10(11) mol/L-1). 3. The RIA established that using KY-mBNP-I was highly sensitive and specific for mBNP, with an IC50 value of 3 fmol/tube and cross-reactivities of less than 0.003% with related natriuretic peptides. mBNP-like immunoreactivity (mBNP-LI) was detected in the mouse atrium (0.35 +/- 0.02 nmol/g), ventricle (20.5 +/- 0.5 pmol/g) and kidney (0.50 +/- 0.05 pmol/g), but not in other tissues including brain. 4. Gel filtration analysis revealed that the major component of tissue mBNP-LI was co-eluted with synthetic mBNP[77-121], a 45-amino acid mature peptide. 5. The monoclonal antibody and RIA for mBNP established here will provide useful tools to investigate the functional significance of BNP in mice, coupled with the genetic engineering approach.

Animals↗

PubMed1994

Angiotensin converting enzyme and genetic hypertension: cloning of rat cDNAs and characterization of the enzyme.

Using genetic mapping approaches, a gene on chromosome 10, Bp1, has been identified in the stroke-prone spontaneously hypertensive rat (SHRSP) in the same region that contains the gene for angiotensin converting enzyme (ACE). Since ACE plays an important role in blood pressure regulation, the ACE gene is a leading candidate for Bp1. To examine the possibility that a structural abnormality of ACE exists in the SHRSP, we cloned and characterized the cDNAs for the Wistar-Kyoto rat (WKY) and SHRSP ACE. Both cDNAs encode a single polypeptide of 1,313 amino acid residues with an estimated molecular weight of 150.9 KDa. Five nucleotide differences were identified between the WKY and the SHRSP ACE cDNAs. One of these differences resulted in an amino acid substitution (Lys-207 in the WKY to Arg-207 in the SHRSP). But the enzymatic properties of partially purified ACE from the two strains were similar. Thus the data suggest that an alteration in the primary structure of rat ACE does not contribute to the hypertension in the SHRSP.

Amino Acid Sequence↗

PubMed1994

Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.

BACKGROUND: B-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure. METHODS AND RESULTS: We measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL), but there was a highly significant step-up of the level between the AIV and the coronary sinus (32.2 +/- 17.0 pg/mL versus 371.4 +/- 111.1 pg/mL, P < .001). In contrast, there was a significant step-up of the plasma BNP level between the aortic root and the AIV (8.6 +/- 6.4 pg/mL versus 19.0 +/- 11.5 pg/mL, P < .01) but not between the AIV and the coronary sinus (19.0 +/- 11.5 pg/mL versus 28.8 +/- 14.0 pg/mL). On the other hand, in patients with dilated cardiomyopathy, there was a significant step-up in the plasma ANP level between the aortic root and the AIV (280.6 +/- 183.7 pg/mL versus 612.3 +/- 431.6 pg/mL, P < .01) and between the AIV and the coronary sinus (612.3 +/- 431.6 pg/mL versus 1229.0 +/- 772.7 pg/mL, P < .01). There was a significant step-up in the plasma BNP level between the aortic root and the AIV (268.4 +/- 293.2 pg/mL versus 511.6 +/- 458.1 pg/mL, P < .01) but not between the AIV and the coronary sinus (511.6 +/- 458.1 pg/mL versus 529.7 +/- 455.3 pg/mL) in patients with dilated cardiomyopathy. The arteriovenous difference at the AIV of the plasma level of BNP had a significant positive correlation with left ventricular end-systolic volume index (r = 0.859, P < .001) and a significant negative correlation with left ventricular ejection fraction (r = -.735, P < .001). CONCLUSIONS: We conclude that (1) BNP is secreted mainly from the left ventricle in normal adult humans as well as in patients with left ventricular dysfunction, whereas ANP is secreted from atria in normal adult humans and also from the left ventricle in patients with left ventricular dysfunction; (2) secretion of BNP as well as ANP from the left ventricle increases in proportion to the severity of the left ventricular dysfunction, suggesting that the secretions of ANP and BNP from the left ventricle are regulated mainly by wall tension of the left ventricle; and (3) the peripheral plasma levels of ANP and BNP reflect the secretion rate of these hormones from the left ventricle and may be used as a marker of the degree of left ventricular dysfunction in patients with left ventricular dysfunction.

Aged↗

PubMed1994

Plasma concentration of atrial natriuretic peptide and brain natriuretic peptide during normal human pregnancy and the postpartum period.

Increases in blood volume are observed during normal gestation and these are reversed shortly after delivery. Although both atrial (A-type) natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) have been described, the role of these peptides in pregnancy and the postpartum period are unclear. This study was designed to examine the effects of pregnancy, labour and delivery on plasma levels of ANP and BNP. Plasma levels of ANP and BNP were determined during normal pregnancy, 30 min after separation of the placenta (immediately postpartum) and between 5 and 72 h postpartum (late postpartum; puerperium). Since the assay sensitivity was 20 pg/ml plasma (for both ANP and BNP), values less than this were assigned a value of 20 pg/ml to calculate means. Plasma levels of ANP and BNP were significantly higher at term pregnancy than during the first trimester (ANP increased from 20 +/- 0.2 to 57 +/- 10 pg/ml (S.E.M.), P < 0.001; BNP increased from 25 +/- 2 to 49 +/- 9 pg/ml, P < 0.01). The plasma level of ANP then rose to 157 +/- 38 pg/ml 30 min after separation of the placenta, being significantly (P < 0.01) higher than that seen at term pregnancy. It declined significantly (P < 0.001) to 32 +/- 3 pg/ml in the late postpartum period. In contrast, the plasma level of BNP 30 min after separation of the placenta was 80 +/- 25 pg/ml, and increased to 116 +/- 17 pg/ml in the late postpartum period, significantly (P < 0.01) higher than the level at term pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[A case of malignant lymphoma, highly suspected to be of pancreatic origin, with multiple nodular hepatic invasions].

We reported a rare case of malignant lymphoma, highly suspected to be of pancreas origin with multiple nodular hepatic invasions. A 63-year-old man visited our hospital on May 24 1990, complaining of anorexia. In spite of high serum levels of LDH and amylase, abdominal ultrasonography (US) showed no significant lesions. Forty days later, he was admitted because of the loss of weight and the appearance of abdominal pain with marked hepatomegaly, exhibiting cachexia. Abdominal US and computed tomography visualized a tumor of pancreas with multiple nodular space-occupying lesions in the liver. In several days, jaundice and ascites appeared with progressive deterioration. Angiography showed no tumor vascularity nor vascular stain in pancreas and liver, suggesting a non-epithelial malignancy. Mitomycin C and Epi-adriamycin, given to the patient via the celiac artery, brought about a remarkable shrinkage of the abdominal tumor. Subsequent systemic chemotherapies and occasional intra-arterial chemotherapies resulted in the disappearance of abdominal tumor clinically. However, at the end of April 1991, signs of CNS involvement were observed, and he died on June 7, 1991. Autopsy revealed that malignant lymphoma, of diffuse large cell type, had invaded the subarachnoidal cavity without any evidence of invasion of the abdomen or other sites except regional necrotic lesion in the pancreas. These findings strongly suggested that the patient suffered from malignant lymphoma of pancreas origin with multiple nodular hepatic invasions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Molecular biology of angiotensin receptors: target for drug research?

UNLABELLED: Angiotensin II receptors: Angiotensin II is a key regulator of cardiovascular homeostasis. At least two distinct angiotensin II receptor subtypes are defined, on the basis of their differential pharmacological and biochemical properties, and designated as type 1 (AT1) and type 2 (AT2) receptors. AT1 subtypes: Recent cloning has revealed that the AT1 type belongs to a seven-transmembrane, G protein-coupled receptor superfamily. The AT1 receptor comprises two isoforms, AT1a and AT1b, which are strikingly similar in amino acid structure, pharmacological specificity and signal transduction mechanism. To date, the evidence indicates that almost all of the known effects of angiotensin II in adult tissues are attributable to the AT1 receptor. AT2 subtype: Much less is known about the function of the AT2 receptor, but its abundant expression in fetal tissues, immature brain, skin wounds, and atretic ovarian follicles suggest that it affects growth and development. The AT2 receptor complementary (c)DNA has recently been cloned. It encodes a 363 amino acid protein with unique tissue distributions and developmental patterns. It is 34% identical in sequence to the AT1 receptor, sharing a seven-transmembrane domain topology. CONCLUSIONS: Further research in defining the functions of the AT1 and AT2 receptor subtypes in cardiovascular regulation will provide new opportunities for new drug discovery and for the characterization of angiotensin II antagonists.

Angiotensin II↗

PubMed1993

Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor.

A cDNA clone encoding the mouse angiotensin receptor subtype 2 (AT2 receptor) was isolated from a mouse fetal cDNA library. Mouse AT2 receptor full-length cDNA contains a 1089-base-pair open reading frame which encodes a protein of 363 amino acid residues. Hydropathy analysis reveals seven putative transmembrane domains. Specific binding of [125I]CGP42112A was demonstrated in membranes of COS-7 cells transfected with the cDNA. Scatchard analysis and ligand displacement profile were typical of the AT2 receptor. Northern blot and reverse transcription-polymerase chain reaction analyses demonstrated that AT2 receptor mRNA was expressed abundantly in fetus and in a lesser amount in adult brain. Analysis of the mouse AT2 receptor gene reveals that the mouse AT2 receptor locus exists as a single copy in the genome, and that the gene does not contain introns in the coding region.

Angiotensin II↗

PubMed1993

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↗

PubMed1993

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress.

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

Atrial Natriuretic Factor↗