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Biomedical subjects

M Szücs

Publications and source records attributed to M Szücs.

At least 19 recordsLinked to original sources
PubMed2002

Chronic morphine-induced changes in mu-opioid receptors and G proteins of different subcellular loci in rat brain.

Prolonged exposure to opioid agonists can induce adaptive changes resulting in tolerance and dependence. Here, rats were rendered tolerant by subcutaneous injections of increasing doses of morphine from 10 to 60 mg/kg for 3, 5, or 10 consecutive days. Binding parameters of the mu-opioid receptor in subcellular fractions were measured with [(3)H]DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin). Although the density of surface mu-sites did not change after the 5-day morphine treatment, up-regulation of synaptic plasma membrane binding was detected after the 10-day drug administration. In contrast, the number of mu-binding sites in a light vesicle or microsomal fraction (MI) was elevated by 68 and 30% after 5 and 10 days of morphine exposure, respectively. The up-regulated MI mu-sites displayed enhanced coupling to G proteins compared with those detected in saline-treated controls. Pertussis toxin catalyzed ADP ribosylation, and Western blotting with specific antisera was used to quantitate chronic morphine-induced changes in levels of various G protein alpha-subunits. Morphine treatment of 5 days and longer induced significant increases in levels of Galpha(o), Galpha(i1), and Galpha(i2) in MI fractions that are part of an adaptation process. Up-regulation of intracellular mu-sites may be the result of post-translational changes and in part de novo synthesis. The results provide the first evidence that distinct regulation of intracellular mu-opioid receptor G protein coupling and G protein levels may accompany the development of morphine tolerance.

Analgesics, Opioid↗
PubMed2001

Ovarian sex steroid-dependent plasticity of nociceptin/orphanin FQ and opioid modulation of spinal dynorphin release.

Pregnancy and its hormonal simulation via 17beta-estradiol (E(2)) and progesterone (P) are associated with spinal opioid antinociception, primarily driven by augmented dynorphin/kappa-opioid activity. This study addresses the ovarian sex steroid-activated mechanism(s) that underlie this activation using an ex vivo spinal cord preparation. In lumbar spinal cord obtained from control animals, exogenous kappa- or delta-opioid agonists (but not mu), as well as nociceptin (orphanin FQ; N/OFQ), dose dependently inhibit the stimulated release of dynorphin. Consistent with these observations, stimulated dynorphin release is enhanced following selective blockade of opioid or N/OFQ receptors, indicating that their endogenous ligands are negative modulators of dynorphin release. In lumbar spinal cord obtained from ovariectomized animals exposed to pregnancy blood levels of E(2)/P, basal and stimulated rates of dynorphin release increase approximately 2-fold. Moreover, evoked dynorphin release is no longer negatively modulated by kappa- or delta-opioid agonists or N/OFQ. Interestingly, in these preparations, release can be facilitated by delta-opioid receptor activation, and neither spinal opioid nor N/OFQ receptor blockade enhances evoked dynorphin release. Consistent with these observations, guanosine-5'-O-3-[(35)S]-thio triphosphate binding analyses indicate a reduction in functional N/OFQ receptors. These data indicate that at least part of the E(2)/P-induced augmented activity of lumbar dynorphin neurons results from their disinhibition via the removal of negative opioid and N/OFQ modulation. These results underscore the plasticity of spinal opioid and N/OFQ systems and their dependence on the ovarian sex steroid milieu. Ovarian sex steroid-activated antinociception reveals mechanisms that enable sustained opioid activation without concomitant tolerance formation.

Animals↗
PubMed2000

Overexpression of dynamin is induced by chronic stimulation of mu- but not delta-opioid receptors: relationships with mu-related morphine dependence.

Several studies using selective opioid agonists or mice with a deletion of the mu-opioid receptor, have shown that morphine dependence is essentially due to chronic stimulation of mu- but not delta-opioid receptors. Because dependence is assumed to be related to persistent intracellular modifications, we have investigated modifications putatively induced by chronic activation of mu receptors with morphine or selective agonists in vitro in SH-SY5Y cells and in vivo in different strains of mice, including mice lacking the mu-opioid receptor gene. The results show a similar down-regulation and desensitization of mu and delta binding sites, whereas an overexpression of dynamin occurred only with mu agonists, strongly suggesting the relevance of this up-regulation with the opiate dependence. Moreover, translocation of overexpressed dynamin from intracellular pools to plasma membranes was observed in chronic morphine-treated rats. This recruitment could be critically involved in long-lasting changes such as alterations of axonal transport observed in opioid dependence.

Animals↗
PubMed1998

[Incidence of septal aneurysm and its clinical significance].

The authors performed 451 transesophageal echocardiographic (TEE) investigations over a period of three years and four months. Atrial septal aneurysm (ASA) was found in 40 cases. Of these, protrusion of the atrial septum towards the right atrium was observed in 17 cases, whilst oscillation of the atrial septum was noted in 23 cases. ASA was associated with patent foramen ovale (PFO) in ten patients, with type II. ASD in nine patients, with other congenital heart disease in six patients, and with other organic heart disease in eight patients. In three cases either an embolus or a tumor was detected in the left atrium, whilst in four cases with ASA there were no other organic cardiac disorders found. In ten patients there was a history of cerebral embolisation. Of these two had chronic atrial fibrillation, whilst the others had sinusrhythm. Of those who had cerebral embolisation, four patients had PFO, one patient had left atrial and auricular thrombi, whilst in four patients various organic heart problems (ischemic heart disease, left ventricular hypertrophy) were detected. In one patient with ASA there was no other cardiac abnormality detected. The authors conclude that ASA, which is often associated with PFO and ASD (in 25.0% and 22.5% of their cases, respectively) is detected in around eight percent of the patients who undergo TEE. ASA particularly when associated with PFO should be considered as a potential source of cerebral emboli. Indeed, cerebral embolisation occurred in 25% of their patients with ASA. It is recommended, that patients with ASA are treated with acetyl salicylic acid, whilst in patients with ASA and PFO anticoagulant therapy is the treatment of choice. In case of cerebral embolisation, or repeated cerebral ischemic attacks, operative interventions should be considered.

Echocardiography, Transesophageal↗
PubMed1998

Receptor-mediated activation of G-proteins by kappa opioid agonists in frog (Rana esculenta) brain membranes.

This study delineates the heterotrimeric guanine nucleotide binding regulatory protein (G-protein) types in frog (Rana esculenta) brain membranes and their activation by kappa opioid agonists. Ethylketocyclazocine (EKC), trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)b enzeneacetamide (U-50,488) and bremazocine displayed dose-dependent, norbinaltorphimine-reversible stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding in crude membrane preparations. G-proteins were identified by Western-blotting using previously characterized specific antisera that were generated against mammalian G-protein alpha-subunits and beta-subunits. A photoreactive guanosine 5'-triphosphate (GTP) analog, [alpha-32P]GTP azidoanilide ([alpha-32P]AA-GTP) irreversibly labeled four proteins in the molecular weight range of 39-43 kDa. Ethylketocyclazocine and U-50,488 stimulated photolabelling of these proteins among which the 39 kDa band comigrated with the protein specifically labelled with the alpha(i2) antibody and the 40 kDa band was identified as alpha(o1). The other two bands were also stained with the alpha(common) antibody, but were not further identified. These results suggest that the endogenously expressed kappa opioid receptors that are present in frog brain interact with multiple G-proteins in situ. Furthermore, the structure of most G-proteins seems to be well preserved during phylogenesis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Synthesis and opioid binding activity of dermorphin analogues containing cyclic beta-amino acids.

In the present work, eight conformationally constrained analogues of the mu specific opioid peptide dermorphin were synthesized by replacing D-Ala2 with stereoisomers of beta-amino-cycloalkane or cycloalkene carboxylic acids. The resulting peptides were tested for their potency to mu and delta opioid binding sites of rat brain membranes labelled with [3H]Tyr1-D-Ala2-MePhe4-Gly-ol, [3H]DAMGO and [3H]Ile5,6deltorphin, respectively. All of the new derivatives displayed highly attenuated binding to both receptor types, albeit the decrease in their potency seemed to be less in the case of delta binding. Trans position of the beta-amino groups resulted in higher binding affinities than that of the corresponding cis isomers, the latter being more flexible than the former. It is concluded that conformational constraints caused either by a rigid ring structure or cis isomers instead of D-Ala2 in dermorphin-derived peptides are unfavourable for binding activity to either opioid receptors. We propose that interaction of the larger heptapeptide derivatives of dermorphins with the mu receptor is distinct from that of the tetrapeptide morphiceptin.

Amino Acids, Cyclic↗
PubMed1995

Effects of testosterone on the rat renal medullary vasopressin receptor concentration and the antidiuretic response.

The renal concentrating ability declines with age in humans and animals. Studies suggest that the concentrating defect is due to a decrease in renal vasopressin sensitivity. With ageing, expression of the renal vasopressin V2 receptor in rat is impaired; the normal receptor expression is restored by testosterone treatment. The effect of testosterone on the renal sensitivity to vasopressin was investigated in young rats. Male rats after orchidectomy and chronic antiandrogen cyproterone acetate treatment, and female rats after chronic testosterone phenylpropionate treatment, were used. The plasma arginine-vasopressin (AVP) and testosterone concentrations, and the antidiuretic responses to AVP and the V2 agonist deamino-[8-D-arginine]-vasopressin (dDAVP) after volume loading were measured, and the renal [3H]AVP binding density was determined. The plasma AVP level decreased slightly, but not significantly, in male rats after orchidectomy and cyproterone acetate treatment, but did not alter in female rats after testosterone treatment. The AVP and dDAVP sensitivities decreased in male rats after orchidectomy and cyproterone acetate administration, and increased in female rats treated with testosterone, as compared with the animals with a normal gonadal function. [3H]AVP binding to the renal inner medullary membranes was decreased following orchidectomy or antiandrogen treatment in male rats, and increased in testosterone-treated female rats. The results suggest that testosterone may play a physiological role in maintenance of the V2 vasopressin receptor expression and hence in the normal urinary concentrating ability in rat.

Androgen Antagonists↗
PubMed1993

[Successful shock wave monotherapy of coral-shaped calculi in the kidney calix].

Authors reported about two patients with staghorn calculi, who have been treated by extracorporeal shock wave monotherapy by Direx Tripter-X-1 Lithotripter. They used in the first case percutaneous nephrostomy, in the second double J catheter as auxiliary method. Patients were treated 3 and 4 time, and they were stone free at three month follow up.

Adult↗
PubMed1993

Epidermal growth factor-like activity and epidermal growth factor-receptors in human primary breast cancer.

Ligands binding to epidermal growth factor-receptors (EGF-Rs) as epidermal growth factor-like activity (EGF-like activity), along with EGF-R levels, were determined from human primary breast cancer samples. Receptor analysis revealed a single class of high affinity binding sites. Ng/mg protein EGF-like activity quantities were measured in cytosols, and were inversely correlated with EGF-R contents (p < 0.01), estimated by two-point assays.

Breast Neoplasms↗
PubMed1992

[Experience with the Direx Tripter X-1].

In nonselected patients 81.5% stone-free rate could be reached in 3 months. In authors's opinion Direx Tripter X-1 is suitable in the treatment of renal and ureteral calculi. They treated staghorn calculi by ESWL monotherapy with success. The Direx lithotripter was found to be effective and easy to operate; the potential cost reduction is of great significance. The treatment requires general anaesthesia and the equipment causes significant noise. After all, Direx lithotripter is a useful machine in the armamentarium of stone disease treatment.

Adolescent↗
PubMed1992

Differential coupling of opioid binding sites to guanosine triphosphate binding regulatory proteins in subcellular fractions of rat brain.

In this study, we present evidence for the occurrence of mu, delta, and kappa opioid binding sites in synaptic plasma membranes (SPM) and microsomes of rat brain. Binding to all three opioid classes was inhibited by 5'-guanylylimidodiphosphate (Gpp[NH]p) in SPM, while microsomal sites proved to be insensitive to this GTP analog. Sensitivity was restored upon solubilization of microsomes with digitonin, suggesting that opioid receptors are physically separated from G proteins in this fraction. Modulation of microsomal binding by Na+ and Mn++ was greater than that of SPM. Pertussis toxin-catalyzed adenosine diphosphate (ADP) ribosylation revealed the presence of G proteins with alpha-subunit molecular weights of 40 kDa in both subcellular fractions. Basal low Km GTPase activity in SPM was greater than in microsomes. Etorphine elicited a concentration-dependent stimulation of guanosine triphosphatase (GTPase) activity in SPMs but not in microsomes, indicating functional coupling of opioid receptors to G protein in the former and an uncoupling in the latter. Microsomes from 3-day-old rat brain contained more mu opioid sites and they were more sensitive to Gpp(NH)p inhibition than those in adults. These results are consistent with the hypothesis that opioid binding sites in adult microsomes are internalized and G protein uncoupled, while those in neonates are newly synthesized, coupled receptors.

Adenosine Diphosphate↗
PubMed1992

Experience with the Direx Tripter X-1 shock-wave lithotripter.

The authors give account of the experience they gained with the Direx Tripter X-1 (ESWL) apparatus. In a random material they succeeded to render 81.5% of the patients stone free within three months. They judge the apparatus suitable for in situ treatment of pelvic and ureteric stones and for the monotherapy of staghorn calculi. It is easy to handle, inexpensive to buy and maintain but noisy to operate, moreover the patient has to be anaesthetized. All in all it is highly useful in the treatment of renal lithiasis.

Adolescent↗
PubMed1992

Species differences in the stereoselectivity of kappa opioid binding sites for [3H]U-69593 and [3H]ethylketocyclazocine.

Stereoselectivity of the binding sites for the specific kappa-opioid agonist [3H]U-69593, a benzeneacetamido based ligand was investigated in membrane suspension prepared from frog and rat brain, as well as guinea pig cerebellum, using the pure chiral forms of different unlabelled opiates. The ligand binding sites showed stereospecificity with at least three orders of magnitude differences in the affinities (measured as Ki values) of the opioid stereoisomer pairs both in rat and guinea pig membrane fractions. However, in frog brain membranes there was no substantial difference in potencies of the (-) and (+) isomers competing for the [3H]U-69593 binding sites. Another type of the kappa-site preferring opioid ligand, [3H]ethylketocyclazocine, a benzomorphan derivative was able to discriminate between (-) and (+) forms of the same compounds even in frog brain membrane preparation. Our data concerning binding profile of [3H]U-69593 in frog brain membranes are consistent with the observation that kappa opioid binding sites in frog (Rana esculenta) brain differ from those kappa-sites found in mammalian brains.

Animals↗
PubMed1991

A monoclonal anti-idiotypic antibody to mu and delta opioid receptors.

A mouse monoclonal, anti-idiotypic, anti-opioid receptor antibody (Ab2-AOR) has been generated from monoclonal anti-morphine antibodies (Ab1). Hybridoma culture supernatants were screened by a solid phase radioimmunoassay (RIA), based on their competition with radiolabelled morphine for Ab1. One of the Ab2s that gave a positive RIA also competed at rat brain opioid receptors with tritiated opioid ligands dihydromorphine (DHM), naloxone, etorphine, Tyr-D-Ala-Gly-Phe-D-Leu (DADLE), Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAMGE) and Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE). SDS-PAGE revealed Ab2-AOR to be highly purified after successive affinity and protein A-Sepharose chromatography. Ab2-AOR at concentrations of 10-100 nM competed with both mu- and delta-selective specific ligands for brain opioid receptors. Less than 13 micrograms/ml Ab2-AOR completely inhibited specific opioid radioligand binding to both soluble and membrane-bound opioid receptors. To demonstrate its anti-delta receptor activity further, a double-antibody ELISA procedure was developed that is based on the binding of Ab2-AOR to immobilized NG 108-15 cells (which contain only delta opioid receptors). Dose-dependent, opioid peptide- and opiate alkaloid-competitive binding of Ab2-AOR-containing ascites fluid to NG 108-15 cells was observed. A mu opioid agonist effect was demonstrated for Ab2-AOR, in that it decreased by 70% [3H]thymidine incorporation into DNA of fetal brain cell aggregates. This agonist-like action of Ab2-AOR was blocked by naltrexone. The antibody bound specifically to brain tissue sections and the presence of diprenorphine blocked this interaction. Hence, an Ab2 with mu and delta specificity has been characterized.

Animals↗
PubMed1991

A monoclonal antibody recognizing kappa- but not mu- and delta-opioid receptors.

A monoclonal antibody (mAb), KA8 that interacts with the kappa-opioid receptor binding site was generated. BALB/c female mice were immunized with a partially purified kappa-opioid receptor preparation from frog brain. Spleen cells were hybridized with SP2/0AG8 myeloma cells. The antibody-producing hybridomas were screened for competition with opioid ligands in a modified enzyme-linked immunosorbent assay. The cell line KA8 secretes an IgG1 (kappa-light chain) immunoglobulin. The mAb KA8 purified by affinity chromatography on protein A-Sepharose CL4B was able to precipitate the antigen from a solubilized and affinity-purified frog brain kappa-opioid receptor preparation. In competition studies, the mAb KA8 decreased specific [3H]ethylketocyclazocine ([3H]EKC) binding to the frog brain membrane fraction in a concentration-dependent manner to a maximum to 72%. The degree of the inhibition was increased to 86% when mu- and delta-opioid binding was suppressed by 100 nM [D-Ala2,NMe-Phe4,Gly-ol]-enkephalin (DAGO) and 100 nM [D-Ala2,L-Leu5]-enkephalin (DADLE), respectively, and to 100% when mu-, delta-, and kappa 2-sites were blocked by 5 microM DADLE. However, the mu-specific [3H]DAGO and the delta-preferring [3H]DADLE binding to frog brain membranes cannot be inhibited by mAb KA8. These data suggest that this mAb is recognizing the kappa- but not the mu- and delta-subtype of opioid receptors. The mAb KA8 also inhibits specific [3H]naloxone and [3H]EKC binding to chick brain cultured neurons and rat brain membranes, whereas it has only a slight effect on [3H]EKC binding to guinea pig cerebellar membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Intraoperative injuries during transperitoneal urological operation.

The mechanism of development of 19 severe side-injuries arising during 230 transperitoneal urological operations was analysed. During a total of 158 RLAs performed for testicular tumour, vascular injuries--of the aorta, inferior caval vein and renal vessels--were suffered in 10 cases, and injury of the small intestine in one case. In another case, occidental ligation and transection of the ureter were made. During radical nephrectomy, liver and splenic injuries were inflicted in two cases each. The left renal vein was injured also in two cases. In one case the contralateral ureter was ligated. Disregarding the first five cases, the injuries were always made in cases of tumours. After analysing the mistakes, suggestions were put forward for eliminating these complications.

Blood Vessels↗
PubMed1990

[Double kidney and ureterocele associated with kidney calculi].

The simultaneous occurrence of infrequent alterations--double kidney, ureterocele and calculi--is reported. Following the operation performed in 2 steps the patient became free of complaints and according to the repeated controls the dilatation of the efferent system regressed, no reflux was observed.

Abnormalities, Multiple↗