Lysophosphatidylcholine metabolism and cardiac arrhythmias

1988 ◽  
Vol 66 (2) ◽  
pp. 185-189 ◽  
Author(s):  
Mitch Giffin ◽  
Gilbert Arthur ◽  
Patrick C. Choy ◽  
Ricky Y. K. Man
Keyword(s):  
Guinea Pig ◽  
Cardiac Arrhythmias ◽  
Rat Heart ◽  
Animal Species ◽  
Microsomal Membrane ◽  
Guinea Pig Heart ◽  
Biochemical Basis ◽  
Cardiac Tissues ◽  
Isolated Hearts

The ability of exogenous lysophosphatidylcholine (LPC) to produce electrophysiological abnormalities in cardiac tissues and cardiac arrhythmias in isolated hearts has been well documented. In this study, the arrhythmogenic nature of LPC in the rat, rabbit, and guinea pig hearts was studied. The rat heart was found to be the most susceptible to LPC-induced arrhythmias, while the guinea pig heart was the least susceptible. Perfusion with labelled LPC revealed that the severity of arrhythmias correlates well with the amount of labelled LPC found in the microsomal membrane. The biochemical basis for the differences in the accumulation of LPC in the microsomal membrane of different animal species was investigated. Our results strongly indicate that the LPC level in the microsomal membrane may be regulated by the activity of microsomal lysophospholipase.

scholarly journals A study of the localization of polynucleotide phosphorylase within rat liver cells and of its distribution among rat tissues and diverse animal species

1972 ◽  
Vol 130 (2) ◽  
pp. 355-362 ◽  
Author(s):  
Y P See ◽  
P. S. Fitt
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Rat Heart ◽  
Animal Species ◽  
Physiological Role ◽  
Rat Tissues ◽  
Mitochondrial Enzyme ◽  
Polynucleotide Phosphorylase ◽  
Rat Liver Cells ◽  
Kidney Liver

1. Rat liver polynucleotide phosphorylase was localized in the mitochondrion, but may also occur in the nucleus. 2. The mitochondrial enzyme was found in rat heart, kidney, liver, muscle and spleen. 3. Mitochondrial polynucleotide phosphorylase is also present in calf, chicken, guinea-pig and rabbit liver and in goldfish muscle. 4. A possible physiological role for the enzyme in the control of the intramitochondrial ADP concentration is suggested.

Resistance of endothelial cells to anoxia-reoxygenation in isolated guinea pig hearts

1989 ◽  
Vol 257 (2) ◽  
pp. H488-H493 ◽  
Author(s):  
S. Buderus ◽  
B. Siegmund ◽  
R. Spahr ◽  
A. Krutzfeldt ◽  
H. M. Piper
Keyword(s):  
Endothelial Cells ◽  
Guinea Pig ◽  
Purine Nucleoside Phosphorylase ◽  
Partial Recovery ◽  
Guinea Pig Heart ◽  
Isolated Hearts ◽  
Oxygen Paradox ◽  
Sudden Rise ◽  
Coronary Endothelium ◽  
Energy Dependent

The release of cytosolic enzymes from myocardial and endothelial cells in the anoxic-reoxygenated guinea pig heart was investigated. Isolated hearts were perfused with Tyrode solution in the Langendorff mode. Sixty-minute anoxic perfusion with or without glucose (5 mM) was followed by 15-min normoxic perfusion with glucose. The losses of purine-nucleoside phosphorylase (PNP) from endothelial cells and of lactate dehydrogenase (LDH) and creatine kinase (CK) from the mass of myocardial cells were determined. After 30-min anoxia, the release of LDH and CK but not of PNP increased. Reoxygenation after 60-min anoxia with glucose caused a partial recovery of tissue ATP but also an increase in leakage of LDH (11% of total in 15 min) and CK (10%) and a sudden rise in coronary resistance, indicating contracture development ("oxygen paradox"). PNP release remained low (0.5%). In hearts subjected to glucose-free anoxia, ATP levels did not rise during 15-min reoxygenation, contracture development was delayed, and the release of LDH and CK was diminished (3.1 and 2.7%, respectively). Leakage of PNP was again low (0.5%). The results indicate that cardiomyocytes are more severely injured by anoxia-reoxygenation than the coronary endothelium. The rapidly developing reoxygenation-induced injury of cardiomyocytes seems to be an energy-dependent phenomenon, since it was attenuated in hearts deprived of substrate in anoxia.

scholarly journals Characterization of the inhibition by stilbene disulphonates and phloretin of lactate and pyruvate transport into rat and guinea-pig cardiac myocytes suggests the presence of two kinetically distinct carriers in heart cells

1993 ◽  
Vol 290 (1) ◽  
pp. 249-258 ◽  
Author(s):  
X Wang ◽  
R C Poole ◽  
A P Halestrap ◽  
A J Levi
Keyword(s):  
Guinea Pig ◽  
Cardiac Myocytes ◽  
Rat Heart ◽  
Heart Cells ◽  
Perfused Heart ◽  
Maximal Inhibition ◽  
Guinea Pig Heart ◽  
Concentration Maximum ◽  
Lactate And Pyruvate ◽  
Rat Heart Cells

1. The kinetics of transport of pyruvate (Km 0.20 mM), L-lactate (Km 2.2 mM) and D-lactate (Ki 10.2 mM) into rat cardiac myocytes were studied and compared with those for guinea-pig heart cells [Poole, Halestrap, Price and Levi (1989) Biochem. J. 264, 409-418] whose equivalent values were 0.07, 2.3 and 6.6 mM respectively. Maximal rates of transport were about 5-fold higher in the rat heart cells. 2. 4,4′-Dibenzamidostilbene-2,2′-disulphonate (DBDS), a powerful inhibitor of monocarboxylate transport into erythrocytes [Poole & Halestrap (1991) Biochem. J. 275, 307-312], was found to be a potent but apparently partial inhibitor of lactate and pyruvate transport, with an apparent Ki value at 0.5 mM L-lactate of about 16 microM in both species. Maximal inhibition was 50% and 80% in rat and guinea-pig cells respectively. 3. The maximal extent of inhibition and apparent Ki values were dependent on both the substrate transported and its concentration. Maximum inhibition was less and the Ki was greater at higher substrate concentrations. 4. A variety of other stilbene disulphonates were studied which showed different Ki values and maximal extents of inhibition. 5. Phloretin was a significantly less potent inhibitor of transport into both rat (Ki 25 microM) and guinea-pig (Ki 16 microM) heart cells than into rat erythrocytes (Ki 1.4 microM). In the rat but not the guinea-pig heart cells, inhibition appeared partial (maximal inhibition 84%). 6. We demonstrate that our results can be explained by the presence of two monocarboxylate carriers in heart cells, both with Km values for L-lactate of about 2 mM and inhibited by alpha-cyano-4-hydroxycinnamate, but with different affinities for other substrates and inhibitors. One carrier is sensitive to inhibition by stilbene disulphonates and has lower Km values for pyruvate (0.05-0.10 mM) and D-lactate (5 mM), whereas the other has higher Km values for pyruvate (0.30 mM) and D-lactate (25 mM), and is relatively insensitive to stilbene disulphonates. Rat heart cells possess more of the latter carrier and guinea-pig heart cells more of the former. 7. The significance of these results for the study of lactate transport in the perfused heart is discussed.

scholarly journals STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN

1967 ◽  
Vol 126 (6) ◽  
pp. 1079-1086 ◽  
Author(s):  
Peter F. Bonventre ◽  
John G. Imhoff
Keyword(s):  
Protein Synthesis ◽  
Guinea Pig ◽  
Cell Cultures ◽  
Diphtheria Toxin ◽  
Neonatal Rat ◽  
Heart Cell ◽  
Heart Cells ◽  
Guinea Pig Heart ◽  
Cardiac Tissues ◽  
Toxin Protein

Primary heart cell cultures of embryonic guinea pigs and the neonatal rat were established and incubated with purified diphtheria toxin. The rat heart cell cultures were refractory to the effects of the toxin; protein synthesis proceeded normally as measured by the incorporation of tritiated leucine into cell proteins; beating heart cells continued to contract; and the cell monolayers remained intact after exposure to the toxin for periods as long as 72 hr. These findings are compatible with the species resistance of the rat to diphtheria toxin. The guinea pig heart cell cultures were found to be extremely sensitive to the toxin. Protein synthesis was inhibited by approximately 50% after incubation with small quantities of toxin for 3 hr. Increasing the concentration of the length of exposure to the toxin did not increase this inhibition significantly. In addition, diphtheria toxin exerted a true cytopathic effect on the guinea pig heart cells. Monolayers were destroyed when incubated with the toxin for 2 to 3 days. The results show that the heart cells reflect species resistance or sensitivity to diphtheria toxin in the absence of neural or endocrine influences and suggest further that the toxin exerts a direct toxicity to muscle cells of the heart. It is not yet possible to explain in biochemical terms why the toxin seems to act specifically on cardiac tissues.

P698The KCa2 channel inhibitor AP14145, but not dofetilide or ondansetron, provides functional atrial selectivity in guinea pig hearts

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B H Bentzen ◽  
J E Kirchhoff ◽  
M A Skarsfeldt ◽  
L Abildgaard ◽  
N Edvardsson ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Guinea Pig ◽  
Ex Vivo ◽  
Pig Model ◽  
Patch Clamp Technique ◽  
Guinea Pig Heart ◽  
Ventricular Repolarisation ◽  
Isolated Hearts ◽  
Guinea Pig Model

Abstract Background and purpose Prolongation of cardiac action potentials is considered antiarrhythmic in the atria but can be proarrhytmic in ventricles if the current carried by Kv11.1-channels (IKr) is inhibited. The current mediated by KCa2-channels, IKCa, is considered a promising new target for treatment of atrial fibrillation. Selective inhibitors of IKr— (dofetilide) and I-KCa (AP14145) were used to compare the effects on ventricular and atrial repolarisation. Ondansetron which has been reported to be a potent blocker of both IKr and IKCa was included to examine its potential atrial antiarrhythmic properties. Methods The expression of KCa2- and Kv11.1-channels in the guinea pig heart was investigated using qPCR. Whole-cell patch clamp technique was used to investigate the effects of dofetilide, AP14145, and ondansetron on IKCa and/or IKr. The effect of dofetilide, AP14145, and ondansetron on atrial and ventricular repolarisation was investigated in isolated hearts. A novel atrial paced in vivo guinea pig model was further validated using AP14145 and dofetilide. Results AP14145 increased AERP (29 ms ex vivo and 38 ms in vivo) without prolonging QTcB both ex vivo and in vivo. In contrast, dofetilide increased QTcB (41 ms) and, to a lesser extent, AERP (16 ms) in isolated hearts and prolonged QTcB (61ms) with no effects on AERP in the in vivo guinea pig model. Ondansetron did not inhibit IKCa, but did inhibit IKr in vitro. Ondansetron prolonged ventricular (25 ms), but not atrial repolarisation ex vivo. Conclusion IKCa inhibition by AP14145 selectively increased atrial repolarisation whereas IKr inhibition by dofetilide and ondansetron increases ventricular repolarisation to a larger extent than atrial repolarisation. Data support that IKCa inhibition may be of value in treating atrial fibrillation without causing adverse effects in the ventricles. Acknowledgement/Funding Innovation Fund Denmark and Wellcome Trust

Nucleoside transport in heart: species differences in nitrobenzylthioinosine binding, adenosine accumulation, and drug-induced potentiation of adenosine action

1984 ◽  
Vol 62 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Evan F. Williams ◽  
Philip H. Barker ◽  
A. S. Clanachan
Keyword(s):  
Guinea Pig ◽  
Rat Heart ◽  
Binding Capacity ◽  
Specific Binding ◽  
Nucleoside Transport ◽  
Inotropic Action ◽  
Guinea Pig Heart ◽  
Cardiac Membranes ◽  
Nucleoside Transport Inhibitors ◽  
Transport Inhibitors

The site-specific binding of the potent and selective nucleoside transport inhibitor, [3H]nitrobenzylthioinosine (NBMPR), to the nucleoside transport system of cardiac membranes of several species was investigated. The affinity of [3H]NBMPR for these sites ranged from 0.03 nM in rat to 0.78 nM in dog. The maximal binding capacity of cardiac membranes for [3H]NBMPR was also species dependent and was greatest in bovine and guinea pig heart (2551 and 1700 fmol/mg protein, respectively) and least in rat (195 fmol/mg protein). The affinities of recognized nucleoside transport inhibitors and benzodiazepines for these transport inhibitory sites in guinea pig and rat heart were estimated by studying the inhibition of the site-specific binding of [3H]NBMPR in competition experiments. These values were compared with their inhibitory effects on the transporter-dependent accumulation of [3H]adenosine in guinea pig and rat cardiac muscle segments and with their ability to potentiate the negative inotropic action of adenosine in electrically driven guinea pig and rat left atria. In guinea pig heart, the recognized nucleoside transport inhibitors and benzodiazepines had an order of affinity (dilazep > hydroxynitrobenzylthioguanosine > dipyridamole > hexobendine [Formula: see text] lidoflazine [Formula: see text] flunitrazepam > diazepam > lorazepam > flurazepam) for the NBMPR site which was similar to those for the inhibition of [3H]adenosine accumulation and for potentiation of adenosine action. In contrast, in rat heart, where the maximal binding capacity of [3H]NBMPR was lower (eightfold), the nucleoside transporter dependent accumulation of [3H]adenosine was also lower (sixfold) and the negative inotropic action of adenosine was not significantly potentiated. Furthermore, NBMPR sites in rat heart displayed a significantly lower affinity for hexobendine, dipyridamole, and lidoflazine relative to sites in guinea pig hearts. These data indicate that significant differences in cardiac nucleoside transport systems exist among species with respect to both membrane density and drug affinity. Such differences influence the ability of transport inhibitors to modify adenosine action in these tissues.

Ultrastructure and Drug Metabolism in the Developing Guinea Pig

1973 ◽  
Vol 31 ◽  
pp. 538-539
Author(s):  
W. Kuenzig ◽  
M. Boublik ◽  
J.J. Kamm ◽  
J.J. Burns
Keyword(s):  
Guinea Pig ◽  
Metabolic Activity ◽  
Animal Species ◽  
Adult Animal ◽  
Smooth Endoplasmic Reticulum ◽  
Fetal Life ◽  
Mixed Function Oxidase ◽  
Cytochrome P 450 ◽  
Microsomal Mixed Function Oxidase ◽  
Mixed Function Oxidase Activity

Unlike a variety of other animal species, such as the rabbit, mouse or rat, the guinea pig has a relatively long gestation period and is a more fully developed animal at birth. Kuenzig et al. reported that drug metabolic activity which increases very slowly during fetal life, increases rapidly after birth. Hepatocytes of a 3-day old neonate metabolize drugs and reduce cytochrome P-450 at a rate comparable to that observed in the adult animal. Moreover the administration of drugs like phenobarbital to pregnant guinea pigs increases the microsomal mixed function oxidase activity already in the fetus.Drug metabolic activity is, generally, localized within the smooth endoplasmic reticulum (SER) of the hepatocyte.

Mitochondrial Oxidation of p-N, N-Dimethylamino-β-Phenethylamine (DAPA)

1975 ◽  
Vol 33 ◽  
pp. 458-459
Author(s):  
W. Allen Shannon ◽  
Hannah L. Wasserkrug ◽  
andArnold M. Seligman
Keyword(s):  
Guinea Pig ◽  
Oxidase Activity ◽  
Amine Oxidase ◽  
Histochemical Demonstration ◽  
Guinea Pig Heart ◽  
Pig Kidney ◽  
Cytoplasmic Vacuoles ◽  
Liver And Kidney ◽  
Mitochondrial Oxidation ◽  
Amine Oxidase Activity

The synthesis of a new substrate, p-N,N-dimethylamino-β-phenethylamine (DAPA)3 (Fig. 1) (1,2), and the testing of it as a possible substrate for tissue amine oxidase activity have resulted in the ultracytochemical localization of enzyme oxidase activity referred to as DAPA oxidase (DAPAO). DAPA was designed with the goal of providing an amine that would yield on oxidation a stronger reducing aldehyde than does tryptamine in the histochemical demonstration of monoamine oxidase (MAO) with tetrazolium salts.Ultracytochemical preparations of guinea pig heart, liver and kidney and rat heart and liver were studied. Guinea pig kidney, known to exhibit high levels of MAO, appeared the most reactive of the tissues studied. DAPAO reaction product appears primarily in mitochondrial outer compartments and cristae (Figs. 2-4). Reaction product is also localized in endoplasmic reticulum, cytoplasmic vacuoles and nuclear envelopes (Figs. 2 and 3) and in the sarcoplasmic reticulum of heart.

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