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S Hynie

Publications and source records attributed to S Hynie.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Dopaminergic receptors--nomenclature and classification of types and subtypes].

At present, dopamine receptors are divided into two groups, dopamine D1-like receptors and dopamine D2-like receptors. In the study of these receptors, application of molecular biology methods has led to the identification of several structurally distinct subfamilies of receptors. D1-like subfamily contains D2, D3, and D4 receptors. These receptors are the primary targets in treatment of schizophrenia, Parkinson's disease and Huntington's chorea. Some of the neuroleptics have very selective action on certain subtypes of dopamine receptors, however, it seems that the efficient treatment of e.g. schizophrenia can be reached only by drugs which affect not only dopaminergic receptors but also 5-HT and possibly other receptors. It is of interest that the antipsychotic drugs originally led to the discovery of dopamine receptors and their subtypes and now, in turn, these receptors are used to search for more selective drugs with antipsychotic and antiparkinsonic effects.

Animals↗
PubMed1995

[5-hydroxytryptamine (serotonin) receptors--nomenclature and classification of types and subtypes].

5-HT receptors represent a superfamily of receptors with the largest known number of receptor subtypes. At present 15 receptor subtypes of three groups has been recognized. The 5-HT1 subfamily of receptors contains subtypes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F; activation of all of them results in the inhibition of adenylylcyclase. The subfamily of 5-HT2 contains subtypes 5-HT2A, 5-HT2B, and 5-HT2C; their activation leads to the stimulation of PLC. Finally, subfamily of miscellaneous 5-HT receptors contains subtypes 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7; some of them has been cloned, however, our knowledge on their function is still minimal. 5-HT receptors participate in many physiological functions and a disturbance in serotonergic neurotransmission might cause several types of disease. 5-HT plays an important role in depression; to cure this disease, drugs which increase levels of this neurotransmitter are used. A new drug group called Selective Serotonin Reuptake Inhibitors (SSRI) has been recently discovered. These drugs block the reuptake of 5-HT into nerve endings. There is an intensive search for new selective agonists as well as antagonists which could be use not only in the classification of receptor subtypes but which also possess certain therapeutic potential.

Animals↗
PubMed1995

[Purinergic receptors--nomenclature and classification of types and subtypes].

The purpose of this review is to present current knowledge regarding purinergic receptors and their subtypes. The main endogenous ligans for these receptors are adenosine and ATP which are released from cells and neurons under various pathophysiological conditions, and adenine nucleotides which are released as contransmiters together with noradrenaline, acetylcholine and substance P. Purinergic receptors which are present in various tissues and mediate numerous physiological effects can be divided into two main groups, P1 (for adenosine) and P2 (for adenine nucleotides) receptors. Both these types are further divided into subtypes. P1 receptors are better characterized than P2 receptors whose classification must be regarded as tentative rather than definitive. P1 receptors are named according to their natural ligand adenosine as A1, A2a, A2b, A3 and possibly A4 receptors. Their characteristics are summarized in tables which also present the main selective agonists and antagonists of their receptors. Since the classification of P2 receptors is still tenative, their nomenclatue does not follow the exact rules which are provided by IUPHAR. P2 receptors are subdivided into these subtypes: P2X, P2Y, P2U, P2T, P2Z and P2D. The article also lists the main agonists and antagonists for these receptors. The introduction of new selective agonists and antagonists not only helps to classify various receptors subtypes of purinoceptors but it also has a big therapeutic potential for various diseases.

Animals↗
PubMed1995

[Differences in the behavior of organic lesions, immunologic and metabolic parameters in 2 inbred strains of rats].

Two inbred rat strains were obtained by selective breeding and inbreeding: IR (isoprenaline resistant) and IS (isoprenaline sensitive). In addition to known differences between the two strains (1) other differences were found. As compared to IS strain, IR rats were more aggressive and showed more comfort behaviour in open field test. IR rats developed larger stress-induced gastric lesions but smaller heart lesions. They had larger spleen and thymus and more severe arthritis after Freund adjuvans administration. The two strains might be useful in studying the effects of drugs on various pathological processes. Their hybrids are being used to study interrelations between different genetic factors.

Animals↗
PubMed1995

[Nomenclature and classification of membrane receptors and their subtypes].

Present rapid growth of information about receptors for endogenous ligands and drugs requires changes in definitions, nomenclature and classifications of receptors and their subtypes. Receptors are defined as such membrane structures for which we have sufficiently reliable characterization of their structure, transducing mechanisms (mediation of intracellular effects), and selectively acting drugs (operational criterion). This characterization is based on the integrated approach to classification that relies on all three essential criteria. The current classification of membrane receptors is organized by International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). Their conclusions about receptor classifications are regularly published in pharmacological journals and in special publications. List of presently known membrane receptors and their subtypes is provided in this review.

Receptors, Cell Surface↗
PubMed1995

[Adrenergic receptors--nomenclature and classification of the types and subtypes].

The purpose of this review is to present current knowledge regarding adrenergic receptors and their subtypes. These receptors belong to the superfamily of structures with seven transmembrane domains. They are coupled with G-regulatory proteins. Similarly to other membrane receptors, their division is based on three criteria: structural, transductional, and operational. At present, adrenergic receptors are divided into three main groups, depicted as alpha 1, alpha 2 a beta receptors. Receptors alpha 1 and alpha 2 are further divided into additional 4 subtypes, which are marked with upper case subscripts A-D. Receptors beta are subdivided into three types, marked with subscripts 1-3. Classification of adrenergic receptors can be considered as a prototype for classification of other membrane receptors. The significance of all known receptors subtypes is not yet known. Multiple subtypes of adrenergic and also other receptor types exist simultaneously not only in one tissue but also frequently in a single cell where they can exert both synergistic as well as antagonistic effects. The discovery of functions and interactions of individual receptor subtypes represents a big challenge for future studies. Introduction of new selective agonists and antagonists not only helps to classify various receptor subtypes but it also has a big therapeutic potential.

Receptors, Adrenergic↗
PubMed1995

Effects of pertussis toxin treatment of rats on estradiol-induced adenohypophyseal growth reaction and on adrenergic lipolysis.

After long-lasting administration of estradiol (4-6 weeks) in the presence or absence of pertussis toxin treatment we followed up the changes in body weight and adenohypophyseal weight in rats subjected to this treatment. The most striking effect was the potentiating effect of pertussis toxin on the estradiol-induced adenohypophyseal growth reaction. Adenylyl cyclase activity in the adenohypophysis was significantly increased in the estradiol-treated group and the addition of pertussis toxin did not further increase this enzyme activity. The lipolytic activity in adipose tissue exhibited a similar response as adenohypophyseal growth. Adrenergic lipolysis stimulated by pertussis toxin was highly significantly increased in tissues of rats treated with pertussis toxin. Our results show that the estrogen-induced adenohypophyseal growth reaction is highly potentiated by the treatment of rats with pertussis toxin and that this effect is in many aspects similar to that observed in adrenergic lipolysis. It thus seems that both processes might be mediated via a pertussis toxin-sensitive G protein which is involved in inhibitory regulation of adenylyl cyclase.

Adenylate Cyclase Toxin↗
PubMed1994

The concept of application of immobilized and perfused mammalian cells (a bioreactor model) in biomedical research.

An overview of the concept of cellular immobilization and perfusion as a small laboratory bioreactor model is presented. The cellular systems currently used may be described as static. This is due to conditions of hypoxia and waste product build-up that affect cell physiology. Cellular immobilization and perfusion is, therefore, expected to maintain the cells for very long periods of time under approximately physiological conditions. A number of applications of immobilized perfused hepatocytes and other cellular systems such as adipocytes and Sertoli cells are described in addition to various other cell lines. Moreover, it is suggested that the bioreactor may have potential use as a bioartificial organ.

Adipocytes↗
PubMed1994

Preparation of functionally active immobilized and perfused mammalian cells: an example of the hepatocyte bioreactor.

In the present study, a method has been employed for hepatocyte immobilization in agarose threads which allows for cell perfusion. The rat hepatocytes are isolated from the liver. A 1.8% low-gelling agarose solution is prepared in warm Krebs-Henseleit solution. The agarose solution is mixed 1:1 with the hepatocytes and the cells are immobilized in agarose threads by extruding the agarose-cell mixture through cooled Chemfluor teflon (TFE) tubing. Light and electron microscopy studies indicated the integrity of the hepatocytes in the gel matrix. This system allows for liver cell perfusion and viability studies to be carried out non-invasively on the cells and provides data that are comparable to those obtained with a perfused isolated liver. Immobilized hepatocytes are an in vitro system worthy of further evaluation which may be useful in the studies of liver cell metabolism and the response of the liver to foreign chemicals.

Animals↗
PubMed1994

Application of the hepatocytes bioreactor to xenobiotic biotransformation.

This study deals with the application of the previously developed immobilized and perfused isolated hepatocytes as a cellular system for the study of representative phase I and phase II of biotransformation reactions. To illustrate phase I reactions, aminopyrine (0.17-4.25 mmol/l) and hexobarbital (0.2 mmol/l) were selected. For phase II reactions, glutathione transferase activity was evaluated by using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate (0.125-2.0 mmol/l). Formaldehyde, that was formed from aminopyrine, increased steadily in the perfusion medium with time. The perfused hepatocytes eliminated hexobarbital at a much higher rate than the hepatocytes in suspension. At several time points the amount of CDNB-glutathione conjugate formed per one million hepatocytes in the bioreactor was almost twice the amount formed by the hepatocytes in suspension. The present data illustrate the successful application of the hepatocyte bioreactor in phase I and phase II of xenobiotic metabolism and indicate that the cells were metabolically more active than the cells in suspension.

Animals↗
PubMed1994

A preliminary evaluation of drug biotransformation in hepatocytes of genetically defined rat strains.

This study was directed to use the genetically developed isoprenaline-sensitive (S), isoprenaline-resistant (R) and spontaneous hypertensive rats (SHR) as standard diseased animal models for in vitro liver function evaluation of drug biotransformation. Hepatic hexobarbital hydroxylase and glutathione transferase (GST) were evaluated by using hexobarbital and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates, at concentrations of 0.21 mmol/l and 1 mmol/l, respectively. The assay was conducted by using isolated hepatocytes in suspension and hepatocytes in a bioreactor configuration. The data demonstrate that there are certain cellular pharmacokinetic differences in hexobarbital hydroxylase and GST activities in hepatocytes obtained from Wistar, SHR, R and S strains which can be better demonstrated, when using the model of perfused and immobilized hepatocytes.

Animals↗
PubMed1994

Adrenergic lipolysis in immobilized and perfused adipocytes.

The method of cellular immobilization and perfusion was applied to adipocytes. The lipolytic effect of isoprenaline, whose action is produced as a result of receptor-drug interaction, was followed. An agarose solution kept at at 37 degrees C was mixed 1:1 with the cell suspension. Thereafter, adipocytes were immobilized in the agarose threads. The lipolytic effect of 0.1 ml of isoprenaline (1 x 10(-4) mol/l), that was rapidly introduced to the cell perfusion inlet in a non-recirculating system, was monitored by assessing glycerol production. The immobilized and perfused adipocytes exhibited significant lipolytic activity. After reaching the maximum effect, 0.1 ml of propranolol (1 x 10(-3) mol/l) that was applied to the bioreactor inlet, abolished the isoprenaline effect. The present data demonstrate the potential applicability of immobilized perfused adipocytes for various kinds of studies.

Adipocytes↗
PubMed1993

[The effect of therapy with adrenergic beta receptor blockers on myocardial beta adrenergic receptors in children with tetralogy of Fallot].

Seventeen children with tetralogy of Fallot undergoing cardiac surgery were investigated for alteration in myocardial beta-adrenergic receptors (BAR) in dependence on the previous chronic administration with the beta-adrenergic blocker metipranolol. Binding parameters, Bmax (maximal binding capacity) and Kd (dissociation constant), in right ventricular tissue were assessed in direct saturation binding studies using 125I-pindolol. It can be concluded that a) chronic administration of metipranolol to nine patients in usual doses did not change either Bmax or Kd of BAR in the samples of right ventricle, and b) twelve hours interval between last dose of metipranolol and removal of tissue samples is sufficiently long to enable normalization of possible changes in the sensitivity of BAR. This finding is supported by the pot-operative course and the response to dopamine which did not differ in patients treated and untreated with metipranolol in the preoperative period. Thus, our results suggest that there is no apprehension of chronic application of beta-blockers in patients with tetralogy of Fallot which would negatively influence the response to dopamine during the operation and in the postoperative period.

Child, Preschool↗
PubMed1993

[The effect of ascorbic acid on adrenergic lipolysis].

The effect of ascorbic acid on basal and adrenergic lipolysis was studied in rat epididymal adipose tissue in vitro. When adipose tissue was incubated with isoprenaline (ISO) for 1.5 h, the concentration-lipolytic effect curves of ISO were practically the same in the presence or absence of ascorbic acid used in concentration 100 and 1000 micrograms/ml. The lipolytic effect of ISO was not substantially altered even in the experiments in which adipose tissue was incubated with ISO for 4.5 h, but ascorbic acid (1000 micrograms/ml) was added only 1.5 h before the end of incubation. On the other hand, the contact of adipose tissue for 4.5 h with high concentration of ascorbic acid (1000 micrograms/ml) induced significant decrease of maximum adipokinetic effect of ISO. Contrary to catecholamine stimulated lipolysis, the basal rate of lipolysis was enhanced by ascorbic acid. Inhibition of maximum lipolytic effect of catecholamines (isoprenaline and noradrenaline-NOR) and oxedrine (isopropylnoroxedrine) was also seen when adrenomimetics were added to incubation medium 1.5 h before the end of 4.5 h incubation of adipose tissue with ascorbic acid. Decreased reactivity of adipose tissue to catecholamines persisted when the tissue, after 3 h incubation with ascorbic, was transferred into fresh medium with ISO and ascorbic acid. Preincubation of ascorbic acid (3h) in the incubation medium without adipose tissue, followed by subsequent addition of the tissue and catecholamines (NOR, ISO) and 1.5 h lasting incubation, did not influence the adipokinetic effect of NOR and ISO. These facts indicate that ascorbic acid decreases the lipolytic effect of catecholamines as a result of its effect on adipose tissue but not on the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

[3H-dihydroalprenolol binding to beta-adrenergic receptors in adipocyte membrane fractions of rats premedicated with estrogens].

Oestradiol administration in vivo has been shown to potentiate the adrenergic lipolysis in vitro in rat epididymal adipose tissue; one of the possible explanations of this oestradiol effect might be the direct influencing of beta-adrenergic receptors. In order to show this possible mechanism of action, in direct radioligand binding studies we have estimated the specific binding parameters of beta-adrenergic receptors in controls and in vivo pretreated rats by a single dose of oestrogen (200 microgram.kg-1 s.c. 24 hours prior sacrification of rats). Beta-adrenergic receptor binding studies we performed with membrane fraction of homogenates of epididymal adipose cells, the radioligand used was L-[3H]-dihydroalprenolol (3H-DHA). No clear-cut differences in the saturation curves of 3H-DHA were found between control and pretreated oestradiol rats; the density of beta-adrenoreceptors (Bmax) was practically identical (269 v. 270 fmol.mg-1 protein) and also differences in dissociation constants (Kd) of both groups were minimal (1.05 vs. 0.95 nmol.1-1). Minimal differences between control and oestradiol pretreated rats were also found in displacement studies, where the effects of 1-isomers of norepinephrine and epinephrine was tested. Thus, it seems possible that the potentiating effect of in vivo pretreatment by oestradiol on adrenergic lipolysis of epididymal adipose tissue in vitro is not caused by the direct influencing of beta-adrenergic receptors. The explanation of this effect will be necessary to search on other steps of the adrenergic reaction which lead to lipolysis or in influencing other receptors (e.g. alpha-adrenergic receptors).

Adipose Tissue↗
PubMed1993

Effects of pertussis toxin on intraocular pressure and adenylate cyclase activity of ciliary processes in rabbits.

The effects of pertussis toxin on the intraocular pressure (IOP) lowering effect of clonidine and isoproterenol as well as on the inhibitory effects of clonidine and neuropeptide Y on adenylate cyclase activity of ciliary processes were studied in albino rabbits. I.v. administered pertussis toxin elicited transient changes in IOP which, however, returned to control values during 2-3 days. In the following days the IOP lowering effect of the alpha 2-adrenergic agonist clonidine was abolished and that of the nonselective beta-adrenergic agonist isoproterenol was attenuated. At the same time, the inhibitory effects of clonidine and neuropeptide Y on basal as well as stimulated adenylate cyclase activities in homogenates of ciliary processes were grossly diminished. The effects of pertussis toxin on the IOP lowering action of adrenergic agonists and on the inhibitory action of clonidine and neuropeptide Y on adenylate cyclase activity were ascribed to an impairment of the function of a G protein in ciliary processes, probably G(i) protein. It is suggested that the decrease of IOP induced by clonidine is due to inhibition of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1991

Non-synaptic cholinergic modulation of neurogenic twitches of the guinea-pig ileum.

The effect of cholinergic and anticholinergic compounds on conduction of neuronal excitation has been studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment (10 mm) so that the aboral segment might be also invaded, eventually. Drugs were added to the middle segment to affect neuronal propagation (non-synaptic effects) which was monitored by twitch height of the aboral segment. The application of acetylcholine to the middle segment augmented aboral twitches. The effects of nicotine, pilocarpine and oxotremorine were selectively blocked by (+)-tubocurarine, pirenzepine and atropine, respectively. The effect of acetylcholine was suppressed by pirenzepine and atropine and mimicked by doubling of KCl concentration. The effect of acetylcholine may be thus explained by the facilitated propagation of nerve action potentials in partially depolarized cholinergic terminals via stimulation of muscarinic receptors. The adenylate cyclase system is not directly involved in the mechanism of muscarinic facilitation of neuronal propagation in the terminals; however, it may participate in the modulation of a final common effector mechanism.

Acetylcholine↗