Receptor-Cyclase Coupling Protein in Erythrocytes of Patients with Essential Hypertension

1984 ◽  
Vol 67 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Zvi Farfel ◽  
Adrian Iaina ◽  
Haskel Eliahou ◽  
Zohara Cohen
Keyword(s):  
Essential Hypertension ◽  
Antihypertensive Drugs ◽  
Normal Subjects ◽  
Erythrocyte Membranes ◽  
Adrenergic System ◽  
Protein Activity ◽  
N Protein ◽  
Type Ia ◽  
Coupling Protein

1. In order to define the alteration of the function of the adrenergic system in hypertension, we studied directly the receptor-cyclase coupling protein (N protein), which is one of the components of the enzyme adenylate cyclase. 2. N protein was determined in erythrocyte membranes of patients with essential hypertension and normal subjects, with a complementation assay in vitro. Fifteen normal subjects and 18 patients with essential hypertension (eight untreated and ten treated with β-adrenoreceptor blocking drugs alone or in combination with other antihypertensive drugs), and two patients with pseudohypoparathyroidism type Ia (known to have deficient N protein activity), were studied. 3. Erythrocyte N protein activities in the various groups expressed as percentages of the means ± sd of normals were: normal subjects 100 ± 13.7, untreated hypertensive 108.9 ± 20.4, treated hypertensive 104.3 ± 11.3 and pseudohypoparathyroidism type Ia 43%. 4. The difference between N protein activity in the hypertensive patients and normals was not statistically significant. We suggest that the molecular basis for the altered sympathetic responsiveness in essential hypertension may reside in other components of the cyclic AMP protein kinase effector system.

Comparative action of calpain on erythrocyte Ca2+-pumping ATPase in sickle cell anaemia, essential hypertension and kwashiorkor

1990 ◽  
Vol 10 (3) ◽  
pp. 281-291 ◽  
Author(s):  
O. O. Olorunsogo ◽  
F. O. Agbolade ◽  
S. O. Owojuyigbe ◽  
J. A. Adebisi ◽  
A. O. Adebayo ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Sickle Cell ◽  
Sickle Cell Anaemia ◽  
Thiol Group ◽  
Normal Subjects ◽  
Erythrocyte Membranes ◽  
Calpain Activation ◽  
Calcium Dependent ◽  
Degree Of Protection ◽  
Comparative Action

Calpain, a calcium-dependent, neutral cysteine-protease was purified from the erythrocyte cytosol of subjects having essential hypertension (HTN), sickle cell anaemia, (SCA), or kwashiorkor (KWA). Identical electrophoretic mobility on SDS-polyacrylamide gradient gel, sensitivity to micromolar amounts of Ca2+, absolute requirement for a reducing environment and a high susceptibility to inhibition by leupeptin and thiol-group modifying reagents confirm that calpain preparations from these erythrocytes are equivalent to calpain I. Whereas the extent of calpain activation of erythrocyte membrane Ca2+-pumping ATPase of normal subjects was almost equal to that due to calmodulin, calpain activation of the HTN and SCA pump was greater than activation by calmodulin. Like in normal membranes, exogenous calmodulin protected the Ca2+-pumping ATPase of these erythrocytes against calpainization; the degree of protection by calmodulin is least in SCA and HTN. Electrophoretic separation of erythrocyte membranes and the purified Ca2+-pumping ATPase of HTN, SCA and KWA subjects does not indicate the presence of fragments resulting from the proteolytic action of calpain.

scholarly journals A Disruptive Mutation in Exon 3 of the GNAS Gene with Albright Hereditary Osteodystrophy, Normocalcemic Pseudohypoparathyroidism, and Selective Long Transcript Variant Gsα-L Deficiency

2007 ◽  
Vol 92 (5) ◽  
pp. 1764-1768 ◽  
Author(s):  
Susanne Thiele ◽  
Ralf Werner ◽  
Wiebke Ahrens ◽  
Ute Hoppe ◽  
Christine Marschke ◽  
...  
Keyword(s):  
Protein Level ◽  
Splice Variants ◽  
Stop Codon ◽  
Erythrocyte Membranes ◽  
Protein Activity ◽  
Α Subunit ◽  
Biallelic Expression ◽  
Albright Hereditary Osteodystrophy ◽  
Gnas Gene ◽  
Type Ia

Abstract Objective: The GNAS gene encodes the α-subunit of stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. In addition to transcript variants that differ in their first exon due to different promoters, there are two long (Gsα-L) and two short (Gsα-S) splice variants, created by alternative splicing. Heterozygous inactivating maternally inherited mutations of GNAS lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia. Methods and Results: The GNAS gene of a 10-yr-old girl with brachymetacarpia, mental retardation, normocalcemic pseudohypoparathyroidism, and hypothyroidism was investigated. We found a heterozygous insertion of an adenosine in exon 3 altering codon 85 and leading to a frame shift inducing a stop codon in exon 4. Molecular studies of cDNA from blood RNA demonstrated normal, biallelic expression of Gsα-S transcripts, whereas expression of Gsα-L transcripts from the maternal allele was reduced. Immunoblot analysis revealed a reduced Gsα-L protein level to about 50%, whereas the protein level of Gsα-S was unaltered. Furthermore, the Gsα protein activity in erythrocyte membranes was diminished to about 75% of normal. Both the reduced activity and the mutation were also found in the mother and the affected younger brother. Conclusion: This report demonstrates the first evidence for a pathogenic mutation in exon 3 of the GNAS gene. The mutation is associated with a phenotype of Albright hereditary osteodystrophy and pseudohypoparathyroidism type Ia due to selective deficiency of Gsα-L and a partial reduction of Gsα activity.

Contribution of Cardiovascular Reflexes to Differences in β-Adrenoceptor-Mediated Responses in Essential Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 177s-180s ◽  
Author(s):  
G. Jennings ◽  
A. Bobik ◽  
M. Esler ◽  
P. Korner
Keyword(s):  
Heart Rate ◽  
Essential Hypertension ◽  
Dose Range ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Normal Subjects ◽  
Cardiovascular Reflexes ◽  
Similar Dose ◽  
Before And After

1. The responses to stimulation of both cardiac and lymphocyte β-adrenoceptors were studied in 23 normal subjects and 23 with untreated essential hypertension. Lymphocyte cyclic adenosine monophosphate was measured in vitro after incubation with isoprenaline (0.01 μmol/l-10 mmol/l). There were no significant differences between the amount of cyclic adenosine monophosphate generated by lymphocytes in the two groups in the isoprenaline concentration range 0.01 μmol/l-1 mmol/l. 2. In the same subjects we compared cardiac β-adrenoceptor-mediated responses using the change in heart rate after bolus doses of isoprenaline (dose range 0.25–3 μg). In 12 subjects (six normotensive, six hypertensive) we studied the heart rate responses to isoprenaline before and after ‘total’ autonomic block (0.04 mg of atropine/kg and 300 μg of clonidine). The latter permitted assessment of intrinsic cardiac responsiveness after eliminating cardiovascular reflexes. 3. In subjects with reflexes intact the rise in heart rate was significantly greater in normal than in hypertensive subjects at all doses of isoprenaline. Isoprenaline evoked a similar dose-related fall in blood pressure in both groups, which contributed to the reflex drive. After autonomic block the differences in heart rate responses were no longer present. 4. The results indicate that the reduced tachycardia at a given dose of isoprenaline in hypertensive subjects is due to impairment in their baroreceptor—heart rate reflex since this was no longer present after atropine and clonidine. 5. The absence of any intrinsic difference in cardiac β-adrenoceptor responsiveness is in agreement with the results with lymphocytes.

scholarly journals In Silico Evaluation of Cyclophilin Inhibitors as Potential Treatment for SARS-CoV-2

2021 ◽  
Author(s):  
Kyle Laurie ◽  
David Holcomb ◽  
Jacob Kames ◽  
Anton A Komar ◽  
Michael DiCuccio ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cyclophilin A ◽  
Coagulation Factors ◽  
Mortality Rates ◽  
Protein Protein Interactions ◽  
Protein Activity ◽  
N Protein ◽  
Isomerase Activity ◽  
Coagulation Proteins

Abstract The advent of SARS-CoV-2 provoked researchers to propose multiple antiviral strategies to improve patients' outcomes. Studies provide evidence that Cyclosporine A (CsA) decreases SARS-CoV-2 replication in vitro, and decreases mortality rates of COVID-19 patients. CsA binds Cyclophilins, which isomerize prolines, affecting viral protein activity. We investigated the proline composition from various Coronavirus proteomes to identify proteins that may critically rely on cyclophilin’s peptidyl-proline isomerase activity and found the Nucleocapsid (N) protein significantly depends on Cyclophilin A (CyPA). We modeled CyPA and N protein interactions to demonstrate the N protein as a potential indirect therapeutic target of CsA, which we propose may impede coronavirus replication by obstructing nucleocapsid folding. Finally, we analyzed literature and protein-protein interactions, finding evidence that, by inhibiting CyPA, CsA may impact coagulation proteins and hemostasis. Despite CsA’s promising antiviral characteristics, the interactions between cyclophilins and coagulation factors emphasize risk stratification for COVID patients with thrombosis dispositions.

In Vitro Incorporation of Sodium Acetate-l-C14 into Leukocyte Lipids of Normal and Leukaemic Subjects as a Function of Incubation Time

1962 ◽  
Vol 02 (02) ◽  
pp. 165-172
Author(s):  
C Miras ◽  
G Lewis ◽  
J Mantzos
Keyword(s):  
Sodium Acetate ◽  
Linear Part ◽  
Lipid Synthesis ◽  
Normal Subjects ◽  
Cytostatic Agents ◽  
Time Intervals ◽  
Total Blood ◽  
Effect Of Treatment ◽  
Product Relation

Summary1. Separated leukocytes or total blood from normal subjects, untreated leukaemic patients and from leukaemic patients treated with cytostatic agents were incubated with CH3COONa-l-C14. Radioactivity of mixed lipids was measured at standard time intervals.2. The time incorporation curve observed with leukocytes from treated leukaemic patients showed after an initial linear part, a more rapid levelling off than the curves observed with leukocytes from untreated and normal subjects.3. Therefore, an indirect effect of treatment on leukocyte lipid synthesis seems to be present.4. Phospholipid and neutral lipid synthesis by leukaemic leukocytes was also studied. The results give no evidence that these fractions as a whole have any precursor-product relation.

Postural Changes in Essential Hypertension under Treatment and their Effect on the Renogram

1971 ◽  
Vol 10 (01) ◽  
pp. 39-46
Author(s):  
C. Alexandrou ◽  
E. Papadakis ◽  
E. Gyftaki ◽  
J. Darsinos
Keyword(s):  
Renal Function ◽  
Essential Hypertension ◽  
Early Diagnosis ◽  
Postural Hypotension ◽  
Antihypertensive Treatment ◽  
Normal Subjects ◽  
Upright Position ◽  
Postural Changes ◽  
Significant Impairment

SummaryRadioisotope renograms were obtained in the upright and prone position in 9 normal subjects, in 5 patients with untreated essential hypertension and in 21 hypertensives under treatment, showing moderate postural hypotension.No significant renographic change were seen in the two positions in normal subjects and untreated hypertensives. Treated hypertensives with postural hypotension showed significant impairment of renal function in the upright position in 15 cases and no change in 6. Renal creatinine clearance was lower in the group that showed renographic changes. Renography in the upright position is suggested as a convenient test for early diagnosis and follow-up of the adverse effects of antihypertensive treatment.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Blood Clotting ◽  
Normal Subjects ◽  
Chronic Uraemia ◽  
Wall Interaction ◽  
End Stage ◽  
Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

DETERMINATION OF BLOOD CORTICOIDS USING THE IN VITRO RESIN UPTAKE OF 3H-PREDNISOLONE

1968 ◽  
Vol 57 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Hironori Nakajima ◽  
Mitsunori Murala ◽  
Masumitsu Nakata ◽  
Takeshi Naruse ◽  
Seiji Kubo
Keyword(s):  
Thyroid Function Test ◽  
Normal Subjects ◽  
Adrenal Function ◽  
Function Test ◽  
Before And After ◽  
Adrenal Response ◽  
Suppression Test

ABSTRACT The in vitro resin uptake of 3H-prednisolone was used for the determination of blood cortisol after addition of radioactive prednisolone followed by Amberlite CG 400 Type 1 to the test serum, and incubation of the mixture. The radioactivity of the supernatant was compared before and after the addition of the resin. The principle of this method is similar to that of the 131I-triiodothyronine resin uptake for the thyroid function test. The tests for the specificity, reproducibility and sensitivity gave satisfactory results. The mean basal value ± SD of the 3H-prednisolone resin uptake was 35.3 ± 9.2% in normal subjects, and 27.1 ± 4.8% in pregnant women. This method was valid in various adrenal function tests, i. e. the adrenal circadian rhythm, corticotrophin (ACTH) test, dexamethasone suppression test and the adrenal response to lysine-8-vasopressin. It proved to be a sensitive indicator of the adrenal function. These results suggest that this method should be useful for a routine adrenal function test.

Effect of [Asu,]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma

1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  
Keyword(s):  
Body Weight ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Regular Insulin ◽  
Prolactin Release ◽  
Saline Administration ◽  
The Central Nervous System ◽  
Plasma Prl ◽  
Male Subjects

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

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