Biomedical subjects

B Hocher

Publications and source records attributed to B Hocher.

At least 55 records · Page 3Linked to original sources

PubMed1998

Renal endothelin system in polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.

Analysis of Variance↗

PubMed1997

Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.

The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.

Animals↗

PubMed1997

Influence of the renal endothelin system on the autoregulation of renal blood flow in spontaneously hypertensive rats.

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

Animals↗

PubMed1997

The paracrine endothelin system: pathophysiology and implications in clinical medicine.

Apart from the initially described vasoconstriction, endothelins have been shown to cause a variety of biological activities in non-vascular tissues. A rapidly growing body of data supports the concept of endothelin as a paracrine acting hormone. In this review, we will discuss the impact of this local endothelin system for various cardiovascular pathophysiological states, especially atherosclerotic vascular disease, restenosis, myocardial infarction, congestive heart failure, and arterial hypertension. In addition, the endothelin system is a modulator of renal function via its binding to abundant receptors in renal tissue and by the ability of renal endothelial and epithelial cells to synthesize and release endothelin. In the kidney, endothelin may function as a paracrine/autocrine factor in the regulation of renal blood flow, glomerular haemodynamics, and sodium and water homeostasis. The renal endothelin system is involved in kidney diseases such as impaired renal function in liver cirrhosis, cyclosporin toxicity, acute renal failure and renal glomerular and interstitial fibrosis. Therapeutic approaches with new orally active endothelin receptor antagonists are also discussed.

Amino Acid Sequence↗

PubMed1996

Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.

Animals↗

PubMed1996

Characterization of the renal phenotype of transgenic rats expressing the human endothelin-2 gene.

We have previously established a transgenic rat model termed TGR(hET-2)37 overexpressing the human endothelin-2 (ET-2) gene with high renal transgene expression. This renal overexpression is of pathophysiological interest because a long-term activated paracrine renal endothelin system has been implicated in chronic renal failure due to progressive glomerular injury. Therefore, our aim in the present study was to analyze renal transgene expression in detail and address the question of whether transgene expression causes phenotypic and functional changes in the kidney. We used reverse transcription-polymerase chain reaction and in situ hybridization techniques for transgene expression analysis. Tissue ET-2 concentrations were measured with a specific radioimmunoassay. For histological evaluation of renal tissue, all samples were subjected to hematoxylin-eosin and periodic acid-Schiff staining. Renal tissue ET-2 concentrations were significantly increased in TGR(hET-2)37 rats. Using in situ hybridization, we found that the human ET-2 gene was almost exclusively expressed within the glomeruli. The glomerular transgene expression resulted in a significantly increased glomerular injury score and likewise in a significantly increased protein excretion, whereas glomerular filtration rate was not altered. Blood pressure was similar in TGR(hET-2)37 rats and age-matched controls, suggesting that the local changes in the kidney were correlated with paracrine endothelin actions. In conclusion, our study revealed that the major renal expression site of the human ET-2 transgene in TGR(hET-2)37 rats was within the glomeruli and caused the development of glomerulo-sclerosis with significantly increased protein excretion that is independent of blood pressure. We suggest that TGR(hET-2)37 rats are a new monogenetic animal model for study of the paracrine renal endothelin system and its involvement in renal pathophysiology.

Animals↗

PubMed1996

Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats.

OBJECTIVE: The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. METHODS: We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. RESULTS: In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 +/- 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 +/- 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 +/- 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (-18.6 +/- 2.1 and -19 +/- 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+2.8 +/- 0.5 and +3.1 +/- 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY. CONCLUSIONS: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.

Animals↗

PubMed1995

Role of the paracrine liver endothelin system in the pathogenesis of CCl4-induced liver injury.

This study analyzed if the paracrine liver endothelin system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar Kyoto rats were divided into four groups: a bosentan (mixed endothelin ETA and ETB receptor antagonist) treated group with CCl4 intoxication, a vehicle treated group with CCl4 intoxication, a nontreated control group and a bosentan treated control group. Hepatotoxicity was assessed by determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) followed by histopathological examinations. Tissue endothelin-1 concentrations and expression of endothelin receptor subtypes were analyzed. The tissue levels of endothelin-1 in the liver of rats with CCl4 intoxication were significantly higher than those in normal rats. Scatchard analysis revealed no differences in the density and binding constant of endothelin ETA and ETB receptor between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in a significant protection against elevation of ALT, AST, LDH and bilirubin. Histopathological examination of live sections for necrotic, swollen and lipid-laden cells revealed findings that were in agreement with the serum enzyme data. In conclusion, this study showed that the paracrine endothelin system is involved in the pathogenesis of CCl4-induced hepatotoxicity and that the blockade of the stimulated liver endothelin systems reduces CCl4-induced liver injury.

Animals↗

PubMed1995

Gender-dependent disease severity in autosomal polycystic kidney disease of rats.

The impact of gender on the course of chronic renal failure in polycystic kidney disease (PKD) has been under discussion for years. Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied. The aim of this study was to evaluate disease severity according to gender, and the occurrence of anticipation and/or genetic imprinting. Male and female affected PKD rats were crossed with respective Wistar-Ottawa-Karlsburg (WOK) rats. From this P generation 26 affected F1 hybrids were obtained, which were then backcrossed with WOK rats, resulting in 275 backcrosses (BC generation). In BC rats the affected males had a significantly higher kidney weight, worse histology and poorer renal function than the females. In the male, but not the female rats of the BC generation, transmission from an affected F1 mother resulted in significantly higher kidney weight, worse histology and poorer renal function than when the gene was inherited through an affected father. Since at the same time body and kidney weight were higher in the respective unaffected males, the previous effect in the affected rats might be due to a growth factor transferred by the mother's milk. The sex of the P generation had no such impact on these parameters. Thus our data provide no evidence for disease anticipation and genetic imprinting (in the classical sense) in the PKD rats, and the assumption of a gender-dependent disease expressivity is favored.

Animals↗

PubMed1995

Distribution of endothelin receptor subtypes in the rat kidney. Renal and haemodynamic effects of the mixed (A/B) endothelin receptor antagonist bosentan.

The paracrine renal endothelin system has been implicated in acute and chronic kidney diseases. However, there are only few data about the expression of endothelin receptor subtypes and their impact on renal function in the normal rat kidney. Therefore, we analyzed the age-dependent expression of endothelin receptors (endothelin receptor A and B) using Scatchard analysis, in vitro and in vivo receptor autoradiography. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan on haemodynamic and renal function in conscious chronically instrumented rats. The renal endothelin receptor A and endothelin receptor B expression is age-dependent. The relative amount of endothelin receptor A significantly decreased with age, whereas the endothelin receptor B significantly increased with age. Compared to the other renal structures, a high endothelin receptor density (endothelin receptor B >> endothelin receptor A) was seen in the renal tubules and even more in the glomeruli. Bosentan blocks both the pressor and depressor response of endothelin. Blocking of both endothelin receptor subtypes using bosentan without application of endothelin, on the other hand, did not alter blood pressure, heart rate, renal blood flow, water excretion or glomerular filtration rate, but significantly decreased sodium excretion.

Aging↗

PubMed1995

Protective effects of the mixed endothelin receptor antagonist bosentan in rats with CCL4-induced liver injury.

We determined whether the paracrine liver endothelin (ET) system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar-Kyoto rats were divided into four groups: a bosentan-treated group with CCl4 intoxication, a vehicle-treated group with CCl4 intoxication, a nontreated control group, and a bosentan-treated control group. Hepatotoxicity was assessed by determination of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Tissue ET-1 concentrations and expression of endothelin receptor subtypes were analyzed. The liver tissue levels of ET-1 in rats with CCl4 intoxication were significantly higher than in normal rats. Scatchard analysis revealed no differences in the density and binding constants of ETA and ETB receptors between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in significant protection against elevation of ALT, AST, LDH, and bilirubin. In conclusion, this study showed that the paracrine ET system in involved in the pathogenesis of CCl4-induced hepatotoxicity and that blockade of the stimulated liver endothelin system reduces CCl4-induced liver injury.

Animals↗

PubMed1995

Renal endothelin system in rats with liver cirrhosis.

Rats with experimental liver cirrhosis have increased endothelin-1 (ET-1) plasma concentrations and show a tendency toward sodium and water retention. We therefore analyzed the renal ET system in cirrhotic rats and control rats, as the renal ET system is involved in the regulation of water and sodium excretion. Cirrhosis was induced by carbon tetrachloride (CCl4) administration. We analyzed the expression of ET receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma and renal tissue ET-1 concentrations using a specific radioimmunoassay. Furthermore, we analyzed the effects of the nonselective (A/B) ET receptor antagonist bosentan on water and sodium excretion and glomerular filtration rate. Our study revealed an overexpression of the ETB receptor in the renal medulla of rats with liver cirrhosis, whereas the density of ETB receptor in the cortex and the ETA receptor in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. The highest ET-1 concentrations were observed in the renal medulla of cirrhotic rats. Glomerular filtration rate decreased in cirrhotic rats but was not altered after bosentan treatment in cirrhotic and control rats. Bosentan decreased sodium excretion in both cirrhotic and control rats to a similar extent, whereas water excretion was reduced by bosentan only in cirrhotic rats. We therefore suggest that the upregulation of medullary ETB in cirrhotic rats is involved int he regulation of water excretion in rats with CCl4-induced cirrhosis.

Animals↗

PubMed1995

Significance of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats: renal and hemodynamic effects of endothelin receptor antagonists.

The renal endothelin (ET) system has been implicated in the maintenance of hypertension in spontaneously hypertensive rats (SHRs). However, little is known about the expression and cellular distribution of the ET receptor subtypes in the kidney of SHRs. We therefore analyzed the expression of ET receptor subtypes in the kidneys of 16-week-old SHRs. Wistar-Kyoto (WKY) rats served as controls. Furthermore, we investigate the effects of the ETA receptor antagonist BQ 123 and the mixed (ETA/ETB) receptor antagonist bosentan on mean arterial blood pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) in conscious, chronically instrumented rats. In SHRs we found overexpression of the ETA in the glomeruli and smooth muscle cells of intrarenal arteries compared to age-matched WKY rats. Furthermore, our study revealed a pronounced upregulation of the ETB in the glomeruli of SHRs. Blockade of ETA and ETB receptors in SHR with bosentan as well as with BQ 123 led to a significant decrease in MAP and a significant increase in RBF, indicating that the ETA receptor plays a major role in the maintenance of high blood pressure and the regulation of RBF in SHRs. The blockade of both ETA and ETB receptors by bosentan has no further effect on MAP reduction or increase in RBF in SHRs compared to ETA blockade by BQ 123. In contrast, combined blockade of ETA and ETB receptors by bosentan significantly decreased GFR in SHRs, whereas no effect on GFR was observed in WKY rats, suggesting that the glomerular ETB overexpression in SHRs is of pathophysiologic relevance.

Animals↗

PubMed1995

Osmotically induced natriuresis and blood pressure response involves angiotensin AT1 receptors in the subfornical organ.

OBJECTIVE: In the present study we tested the hypothesis of whether the centrally induced natriuresis and blood pressure increase after intracerebroventricular injection of hypertonic saline involves the subfornical organ, as suggested by the occurrence of osmosensitive cells as well as a high concentration of angiotensin II receptors in this brain area. METHODS: All experiments were performed in conscious Wistar rats. A chronic cannula was inserted into the lateral brain ventricle for intracerebroventricular injection and a chronic indwelling intracranial guide cannula for microinjection was placed in the subfornical organ. In addition, the rats were provided with ureter catheters for urine collection. RESULTS: Intracerebroventricular injections of hypertonic saline (0.3 mol/l; n = 7) increased renal sodium excretion from 180.0 +/- 30.0 to 279.0 +/- 34.0 mol/l/60 min (P < 0.001) accompanied by an increase in mean arterial pressure of 8.3 +/- 1.2 mmHg (P < 0.01). No change in urinary volume was observed. After injection of the specific AT1 receptor antagonist, losartan, into the subfornical organ (5 micrograms/200 nl; n = 8) the natriuresis and blood pressure response to intracerebroventricular hypertonic saline was completely abolished. Control injections of losartan into areas adjacent to the subfornical organ had no effect on the responses to hypertonic saline. CONCLUSION: Our results suggest that the centrally induced natriuresis and blood pressure responses to hypertonic saline are mediated by an angiotensinergic mechanism involving the subfornical organ.

Animals↗

PubMed1994

Effect of bacitracin on the degradation of a vasopressin receptor ligand with high affinity for the V1 and V2 vasopressin isoreceptors.

We previously described a new iodinated vasopressin analogue (N epsilon-[125I]L-Tyr-[Lys8]-vasopressin) with high affinity for the vasopressin V1 and V2 isoreceptors. The aim of the present study was: i) to analyse the degradation pathway of N epsilon-[125I]L-Tyr-[Lys8]-vasopressin and (ii) to look for an effective inhibitor of radioligand degradation. N epsilon-[125I]L-Tyr-[Lys8]-vasopressin was processed in a temperature-dependent manner by crude cell membranes from LLC-PK1 cells. Only one degradation product was seen using RP-HPLC. The degradation product co-eluted with monoiodotyrosine. The stereoisomer, N epsilon-[125I]D-Tyr-[Lys8]-vasopressin, underwent the same degradation process. Bacitracin prevented degradation at doses as low as 40 mg/l without alterating the binding affinity.

Animals↗

PubMed1994

Expression of the erb B oncogene in the Morris hepatoma 7777.

Altered expression of protooncogenes/oncogenes is believed to be involved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v-erb B mRNA of normal rat liver with that of Morris hepatoma 7777 using Northern blot analysis and in situ hybridization. Northern blot analysis revealed a strong overexpression of the v-erb B related mRNA, while the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slightly increased number of silver grains in the hepatoma cells compared with normal rat liver. On the other hand, the v-erb B related mRNA was strongly overexpressed in the hepatoma cells, while the connective-tissue capsule, the blood vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained in liver metastases. The detectable v-erb B hybridization signal was lost by pretreatment with RNase A. We conclude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris hepatoma 7777, while the increased expression of the v-erb B related mRNA is due to a selection of ligand-independent tyrosine kinase activity.

Animals↗

PubMed1993

Expression of vasopressin receptors (V2-subtype) on LLC-PK1 cells during cell culture.

Vasopressin receptor expression on LLC-PK1-cells (a porcine renal tubular cell line) during cell culture is still not fully understood. We studied receptor expression using a novel vasopressin analogue with high specific radioactivity ([125I][8-p-hydroxy-phenylpropionyl]-lys8-vasopressin, 74EBq/mol (2000 Ci/mmol)). LLC-PK1 cells were grown in monolayers for 1 to 6 days. Scatchard analysis performed with membranes of LLC-PK1 cells revealed a single binding site with a binding constant (Kd) of 0.46 +/- 0.04 nmol/l. During cell culture, the binding constant (Kd) was not altered, but receptor density increased significantly (21,115 +/- 645 receptors per cell, day 2; 42,315 +/- 1512 receptors per cell, day 6). A receptor occupancy of about 30% was found to be associated with a cAMP stimulation of 50%. The receptor reserve might be even higher because, by using a highly specific oxytocin antagonist, we found that 20% of the occupied [125I][8-p-hydroxy-phenylpropionyl]-lys8-vasopressin-binding sites are oxytocin receptors. For lys8-vasopressin receptor studies, great care has to be taken to examine cells in identical culture phases.

Animals↗

PubMed1993

Influence of dopaminergic agonists/antagonists on fucose metabolism in the rat brain.

UNLABELLED: Valid indications of a key role for dopaminergic drugs in glycoprotein fucosylation in neuronal tissue in vitro led us to investigate whether the administration of dopaminergic agonists/antagonists influences fucose metabolism in the rat brain in vivo. Three test groups were set up. Group 1 was given L-DOPA (210 mg/l), Group 2 haloperidol (10.5 mg/l) in drinking water, Group 3 served as control. The rats were sacrificed after 8 weeks and enzyme activities in 5 different brain areas were determined concerning the enzymes of the anabolic fucose metabolism: fucokinase, fucose-1-phosphate pyrophosphorylase and fucosyltransferase 1 and 2. Only the specific activity of fucokinase was affected by haloperidol or L-DOPA administration. In the olfactory bulbus, thalamus and cortex, haloperidol decreased fucokinase activity by 21%, 37%, and 39%, respectively (p < 0.05 in each case). No changes were observed in the cerebellum and striatum. Surprisingly, fucokinase activity in the cortex was decreased by L-DOPA (31%, p < 0.05). CONCLUSIONS: Cerebral fucokinase activity is influenced in vivo by dopaminergic drugs in well circumscribed brain areas. Other enzymes of the anabolic fucose metabolism showed no change in activity. It is, therefore, conceivable that these drugs, apart from known mechanisms, exert part of their pharmacological action via a modulation of fucose metabolism.

Animals↗