PubMed Health⌕ Search

Biomedical subjects

M Klapperstück

Publications and source records attributed to M Klapperstück.

12 recordsLinked to original sources
PubMed2000

Antagonism by the suramin analogue NF279 on human P2X(1) and P2X(7) receptors.

The effect of the suramin analogue 8,8'-(carbonylbis(imino-4, 1-phenylenecarbonylimino-4,1-phenylenecarbonylimino))bis(1,3 , 5-naphthalenetrisulfonic acid) (NF279) was analyzed on human P2X(1) and P2X(7) receptor subtypes (human P2X(1) and human P2X(7)) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. At activating ATP concentrations of 1 microM (human P2X(1)) and 10 microM ATP (human P2X(7)), IC(50) values of 0.05 microM and 2.8 microM were found for human P2X(1) and human P2X(7) receptors, respectively. An increase in the activating [ATP] shifted the NF279 concentration-inhibition curve rightwards for both receptors. NF279 slowed the activation of both human P2X(1) and human P2X(7) as well as the desensitization of human P2X(1). The data support a model in which desensitization of P2X(1) is dependent on preceding activation of these P2X receptors. It is concluded that NF279 acts as a competitive antagonist with much higher potency at human P2X(1) than at P2X(7) receptors. NF279 may hence be suited to discriminate between both receptors in native tissues.

Animals↗
PubMed1999

The new antiarrhythmic substance AWD 23-111 inhibits the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes.

The effects of N-(dicyclohexyl-carbamoylmethyl)-N-(3-diethylamino-propyl)-4-nitro -benzamide hydrochloride (AWD 23-111), a novel antiarrhythmic compound, were studied in isolated cardiomyocytes of guinea pigs. Using whole-cell configuration of the patch-clamp technique AWD 23-111 was tested for its ability to block the delayed rectifier potassium channel (IK). In guinea pig ventricular myocytes the current is composed of two components: IKr, a rapidly activating current and IKs, a slowly activating component which were discriminated by their different activation and deactivation behaviour. In this preparation AWD 23-111 displayed concentration dependent inhibitory effects on IKr as well as on IKs in the tested concentration range between 1 and 100 mumol/l. This blocking effect was independent of the stimulation frequency (0.2, 1 and 2 Hz). There was no influence of AWD 23-111 on the amplitude of L-type calcium whole-cell currents. The compound significantly prolonged action potential duration (APD) at a stimulation frequency of 2 Hz (1 and 10 mumol/l). At 0.2 Hz there was no effect on APD. Our results suggest that AWD 23-111 blocks both components of IK without a reverse use-dependent effect on APD which limits the therapeutic potential of most other class III agents.

Action Potentials↗
PubMed1997

Purinoceptor-operated cationic channels in human B lymphocytes.

1. Using the patch clamp method in the outside-out configuration, purinoceptor-dependent unitary currents were measured in tonsillar and transformed tonsillar human B lymphocytes. 2. Single channel currents were evoked by ATP4-, the free-acid form of ATP, and by 2',3' O-benzoyl-4-benzoyl-ATP (BzATP) in the micromolar concentration range, but not by 10 mM ADP3- or 0.5 mM Mg(2+)-bound ATP. 3. The channels could be activated and deactivated several times for as long as 30 min even in the absence of intracellular ATP, GTP, or glucose. 4. The channels were selective for small cations and had a conductance of 9 pS with Cs+ as the intracellular and Na+ as the extracellular monovalent cation. 5. The half-maximal activation of the channels was obtained by 114 microM ATP4- and by 16 microM BzATP. The increase in the open probability after raising the ATP4- concentration was mainly due to a decrease in the times the channels spend in the closed state. 6. It is concluded that human B lymphocytes possess cationic channels directly gated by extracellular ATP4-. Their agonist binding characteristics are typical for P2z purinoceptors, but their permeation behaviour is different from the large non-specific pores formed by ATP4- in fibroblasts, macrophages and mast cells.

Adenosine Triphosphate↗
PubMed1995

Nonselective cationic currents elicited by extracellular ATP in human B-lymphocytes.

Adenosine 5'-triphosphate-(ATP)-induced whole-cell currents were studied in human B-lymphocytes, transformed by the Epstein-Barr virus, by means of the tight-seal voltage-clamp technique. During bath application of ATP, the membrane conductance was increased. The change of membrane conductance occurred within milliseconds. The dose response relationship for the ATP(4-)-elicited membrane current (Ip) was fitted by the Hill function with a Hill coefficient of 1 and a KD value of 0.2 mmol/l. Adenosine, as well as the Mg(2+)-bound form of ATP, did not effect the membrane conductance. Ip did not desensitize within 1 min and could be evoked repeatedly up to 100 times in 1 cell in the presence of the G-protein blocker Guanosine 5'-o-(2-thiodiphosphate) (GDP [beta S]). Therefore, it seems that ion channels in form of P2Z-purinoceptors are involved in the observed effects. The permeability (P) sequence for cations carrying Ip was PCa:PK:PCs:PNa:PTRIS = 35:2:1.2:1:0.1. The reversal potential of IP was not changed by substitution of intracellular Cl- for aspartate, indicating that anions are not involved in the purinoceptor-dependent conductance. A single-channel conductance of P2Z-receptor-dependent ion channels of about 3 pS was determined by noise analysis of Ip.

Adenosine Triphosphate↗
PubMed1993

Protection from reperfusion-induced arrhythmias by polyethylene glycol 600.

The effects of polyethylene glycol (PEG) 600 on cardiovascular parameters and reperfusion-induced arrhythmias were investigated using a 5-min period of ligation of the left anterior descending coronary artery followed by reperfusion in an anaesthetized open-chest rat model. PEG 600 was effective in reducing reperfusion arrhythmias, such as ventricular fibrillation and ventricular tachycardia. Mortality was decreased from 29.4% (5/17) in the saline-control to 0% (0/14) in the PEG-treated group (P < 0.05). Biochemical investigations during the ischaemia/reperfusion period revealed that PEG infusion resulted in a reduction of cardiac lactate as well as a striking maintenance of the glutathione content of the heart.

Animals↗
PubMed1991

Carbon disulfide exposure attenuates adrenergic inotropic response in rats.

Catecholamine-induced myocardial necrosis is enhanced in carbon disulfide exposed rats. We investigated whether the reported morphological findings after carbon disulfide exposure are accompanied by functional disturbances of the adrenergic inotropic response as well as by biochemical alterations. The cardiac effects of epinephrine and norepinephrine were studied in urethane-anesthetized rats which had been subacutely exposed to carbon disulfide. Compared with not exposed control animals left ventricular inotropic response was diminished and the transient T-wave elevation of the ECG due to ischemic episodes was enhanced in carbon disulfide-exposed rats. Activity of LDH-isozymes in the myocardium was shifted toward LDH-M. Our results support the hypothesis that carbon disulfide causes disturbances of energy supply in the heart.

Animals↗
PubMed1990

Effects of carbon disulfide on cardiovascular function after acute and subacute exposure of rats.

Epidemiologic studies provided evidence that increased heart disease mortality after carbon disulfide exposure is not only related to carbon disulfide-caused coronary sclerosis but they suggest that there would be reversible, direct cardiotoxic effects. In order to investigate such direct toxic effects of carbon disulfide on the cardiovascular system, in this study carbon disulfide was administered acutely and subacutely to rats. Blood pressure and heart rate in normotensive conscious unrestrained rats were not markedly influenced by both acute and subacute carbon disulfide administration. Depressant effects of carbon disulfide administration on intracardiac impulse generation and conduction as well as on contractile force were observed in urethane-anesthetized rats. The appearance of several forms of aconitine-induced arrhythmias was delayed after subacute treatment with carbon disulfide. In the coronary occlusion model, subacute carbon disulfide treatment reduced the survival rate accompanied by marked influences on arrhythmia development. Our results show that short term carbon disulfide exposure alters cardiac function in rats under physiological and pathophysiological conditions.

Aconitine↗
PubMed1989

[Short term effects of carbon disulfide on the intracardial irritation development and transmission in the rat].

Studies were conducted into effects of acute and subacute CS2 application on intracardiac irritability and conduction in rat. Aconitine-induced arrhythmia and the coronary occlusion method were used as pathophysiological models. Under physiological conditions, short-time exposure to CS2 caused deceleration of intracardiac impulse conduction, while under pathophysiological conditions, modified arrhythmia or reduced survival rate was the result.

Animals↗
PubMed1984

[The PABA test].

PABA test has proved to be an easy and reliable test for determination of exocrine pancreatic insufficiency. N-benzoyl-L-tyrosyl-p-aminobenzoic acid or 4-(N-acetyl-L-tyrosyl) aminobenzoic acid are split by action of chymotrypsin in the small intestine. N.O-diacetyl-L-tyrosyl-p-aminobenzoic acid is converted easy in vivo in 4(N-acetyl-L-tyrosyl) aminobenzoic acid. The amount of 4-aminobenzoic acid (PABA) in urine collected for 6-10 hours is used as an index of chymotrypsin production. The concentration of PABA (and aromatic amines) is estimated in urine by the Bratton and Marshall method. p-dimethylamino cinnamaldehyde is less useful for the determination of urinary PABA. 60 min are necessary as time for acid hydrolysis of conjugated PABA metabolites. False abnormal test results are found for instance in patients with inflammatory bowel diseases, small bowel resection, impaired liver function, anorexia nervosa, lambliasis or renal insufficiency. The PABA test appears in consideration of these restrictions to be an useful simple method in the assessment of exocrine pancreatic function.

4-Aminobenzoic Acid↗