BIOLOGICAL APPLICATIONS OF IONOPHORES: THEORY AND PRACTICE<sup>fn1</sup>

Pressman, Berton C.; deGuzman, Norberto T.

doi:10.1111/j.1749-6632.1975.tb31497.x

Cited by 84 publications

(24 citation statements)

References 22 publications

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“…IONOPHORES such as X537A, monensin, and A23187 have been used in attempts to alter the intracellular concentration of free calcium or sodium in the myocardium and thereby further define the roles of these cations in regulating cardiac function (Holland et al, 1975;Pressman, 1973;Pressman and deGuzman, 1975;Schaffer et al, 1974;Schwartz et al, 1974;Sutko et al, 1977). Of these, A23187 has been shown to have some specificity for calcium, although the ionophore also transports magnesium and hydrogen ions across biological membranes (Reed and Lardy, 1972).…”

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confidence: 99%

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Lindemann¹,

Besch²,

Watanabe³

1979

Circulation Research

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SUMMARY The contractile and biochemical effects of the divalent cation ionophore A23187 were studied in isolated perfused guinea pig and rat ventricles. A23187 increased both cyclic adenosine 3':5'-monophosphate (cyclic AMP) and cyclic guanosine 3':5'-monophosphate (cyclic GMP) concentrations in guinea pig ventricles. Associated with these changes in nucleotide content were positive inotropic effects and activation of giycogen phosphorylase. Pretreatment of «nirrmln with reserpine to deplete endogenous catecholamine stores or pretreatment of hearts with propranolol failed to alter these ionophore-induced change*. In contrast, blockade of histamine (Hi) receptors with metiamide completely abolished the positive inotropic effects and activation of giycogen phosphorylase induced by A23187. In these metiamide-treated hearts, the ionophore-induced increase in cyclic AMP concentration was significantly attenuated, whereas the increase in cyclic GMP content persisted. A23187 produced a negative inotropic effect in hearts taken from rats treated with reserpine. In these rat hearts, cyclic AMP levels and giycogen phosphorylase activity were unchanged, whereas cyclic GMP concentrations were markedly increased. These results indicate that A23187 produces both indirect and direct effects on guinea pig ventricles. The indirect effects are mediated primarily by histamine, presumably released from tissue mast cells by the ionophore. Histamine in turn increases cyclic AMP levels, which leads to activation of phosphorylase and positive inotropic effects. The direct biochemical effect of A23187 is an increase in cyclic GMP concentrations. Ore Rea 44: [473][474][475][476][477][478][479][480][481][482] 1979

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mentioning

confidence: 99%

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Lindemann¹,

Besch²,

Watanabe³

1979

Circulation Research

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“…4 ' 25>2B However, in the intact animal the response pattern is most probably complex and composed of several components. Certainly marked hemodynamic changes occur when X-537A is administered to the intact animal.…”

Section: Discussionmentioning

confidence: 99%

“…4 ' 25 ' 2B The involvement of catecholamines in the response pattern of the intact animal is also uncertain, since other carboxylic ionophores are now known which, although virtually devoid of in vitro catecholamine transport capacity, can have potent cardiovascular activity. 4 The results of the isotopic experiments provide direct evidence that X-537A is indeed capable of modifying membrane permeability in intact tissue. However, they also reveal that in this physiologically perfused situation the permeability changes induced by this ionophore are primarily in regard to K + and Na + .…”

Section: Discussionmentioning

confidence: 99%

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Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium.

Wendt¹,

Langer²

1977

Circulation Research

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SUMMARY The effects of the ionophore X-537A on mechanical function and on ionic exchange were studied in the isolated, arterially perfused rabbit interventricular septum. X-537A produced an initial positive inotropic response which was, however, transient in this preparation and appeared to be dependent on an effect of the ionophore on catecholamines. The positive inotropy gave way to a progressive decline in force development which was unrelated to the action of catecholamines and was not accompanied by the development of contracture. Isotope uptake experiments revealed that coincident with this decline in force development there was a continuous net loss of tissue K + and a net gain of Na*. X-537A (5 (HM) perfused for 20 minutes resulted in a net K + loss of 50.2 ± 4 . 6 mmol/kg dry weight and a net Na" gain of 74.0 ± 4.5 mmol/kg dry weight. Isotope washout experiments confirmed that the entire net loss of K' could be accounted for by increased K + efflux. X-537A did not alter Na + efflux nor did it have any detectable effect on 45 Ca exchange of the perfused septum in which the ability to detect net movements is at a level of approximately ± 550 /*mol/kg dry weight. On removal of the ionophore the decline in force development ceased and reversed to near control levels and the progressive ionic changes ceased. However, despite the near total recovery of contractile function the Na + and K 1 levels remained at values little different from those reached at the termination of X-537A perfusion. In addition, after removal of the ionophore, we found that K + exchange rate remained significantly less than control and, furthermore, a kinetic inhomogeneity of tissue K + was observed. The results emphasize a dissociation between cellular Na* and K + content and function following the ionic perturbations induced by the ionophore.Recently a number of naturally occurring antibiotics have been isolated which modify the permeability of biological membranes. These compounds, commonly referred to as ionophores. form lipid-soluble complexes with certain cations and, since this complexation reaction is dynamically reversible, are able to transport the cations across lipid barriers, including bulk phase model systems and biological membranes. Of the known ionophores X-537 A has perhaps the widest range of ionic selectivity, being able to complex both divalent and monovalent cations as well as organic amines.1 -2>4 Its affinity for divalent cations has prompted its application to the investigation of several Ca 2+ -dependent biological systems. That X-537A can function as a Ca 2+ ionophore at biological membranes is indicated by its ability to enhance Ca 2+ leakage from retinal lipid liposomes.5 to release accumulated Ca 2+ from intact mitochondria "• 7 and sarcoplasmic reticulum vesicles isolated from either skeletal or cardiac muscle.8 "" and under certain conditions to induce Ca 2+ uptake in submitochondrial particles.12 In addition X-537A can stimulate Ca 2+ -dependent secretion from various cells. "19 It is. however, contr...

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“…Liquid membranes have been studied as models of biological membranes and as a mean of performing chemical separations (Pressman and deGuzman, 1975). A liquid membrane is a liquid or quasi-liquid phase that separates two other liquid phases in which the membrane is immiscible.…”

Section: Kinetics Of Cation Transport In the Pressman Cellmentioning

confidence: 99%

Capability of arsonolipids to transport divalent cations: a Pressman cell study

Gortzi

Klepetsanis

Antimisiaris

et al. 2001

Chemistry and Physics of Lipids

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The ability of the newly synthesized arsonolipids (2,3-diacyloxypropylarsonic acids) to transport cations was studied using the Pressman cell. Experimental results demonstrate that arsonolipids are much more efficient carriers of Ca 2 + and Mg 2 + than natural phosphatidic acid in the Pressman cell experiments. The ability of arsonolipids to transfer Ca 2 + is affected by the lipid side chain length in the order: C 12 C 14 $ C 16 . Ca 2 + is transferred faster than Mg 2 + , suggesting that the latter is more tightly bound to the arsonolipids. The transfer kinetic curves are parabolic for C 12 , while initially linear with a tendency to reach a steady state for C 14 and C 16 , when the pH in the donor compartment was 8.3. The transport kinetics for both ions studied were best fitted by an equation derived from saturation kinetics that apply in reversible chemical reactions. The ion transfer rates increased as the pH in the donor compartment decreased.

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BIOLOGICAL APPLICATIONS OF IONOPHORES: THEORY AND PRACTICE^fn1

Cited by 84 publications

References 22 publications

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium.

Capability of arsonolipids to transport divalent cations: a Pressman cell study

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BIOLOGICAL APPLICATIONS OF IONOPHORES: THEORY AND PRACTICEfn1

Cited by 84 publications

References 22 publications

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Indirect and direct effects of the divalent cation ionophore A23187 on guinea pig and rat ventricular myocardium.

Effects of the antibiotic ionophore X-537A on contractility and ionic exchange in rabbit ventricular myocardium.

Capability of arsonolipids to transport divalent cations: a Pressman cell study

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BIOLOGICAL APPLICATIONS OF IONOPHORES: THEORY AND PRACTICE^fn1