Frederick W. Flitney

Publications (4)10.33 Total impact

• Article: Evidence that cyclic GMP may regulate cyclic AMP metabolism in the isolated frog ventricle

  Frederick W. Flitney, Jaipaul Singh
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  ABSTRACT: Both acetylcholine and 8-bromo cyclic GMP depress the contractile response of the isolated frog ventricle. An investigation has been made of the effects of both substances on the metabolism of endogenous 3,5 cyclic nucleotides. The levels of adenosine 3′, 5′ cyclic monophosphate (cyclic AMP) and guanosine 3′, 5′ cyclic monophosphate (cyclic GMP) were measured after superfusing preparations with varying concentrations (10−10 to 10−4m) of acetylcholine and 8-bromo cyclic GMP. The decline in contractile force was found to be accompanied by a progressive fall in intracellular cyclic AMP and a rise in cyclic GMP levels. Both the decline in contractility and the reduction in endogenous cyclic AMP are attenuated by 10−4 theophylline. The decline in isometric twitch tension was paralleled, under all conditions, by a quantitatively equivalent reduction in the ratio cyclic AMP: cyclic GMP. The possibility that endogenous cyclic GMP may accelerate the conversion of cyclic AMP to 5 AMP, by stimulating a cyclic GMP-sensitive form of cyclic AMP phosphodiesterase, is discussed.
  Journal of Molecular and Cellular Cardiology 12/1981; · 5.17 Impact Factor
• Article: Adenosine depresses contractility and stimulates 3′,5′ cyclic nucleotide metabolism in the isolated frog ventricle

  Jaipaul Singh, Frederick W. Flitney
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  ABSTRACT: Adenosine depresses the contractile response of the isolated frog ventricle. An investigation has been made of its effects on the metabolism of endogenous 3′,5′ cyclic nucleotides. The levels of adenosine 3′,5′ cyclic monophosphate (3′,5′ cyclic AMP) and guanosine 3′,5′ cyclic monophosphate (3′,5′ cyclic GMP) were measured at different times during exposure of the ventricle to adenosine (10−3m). The decline in isometric twitch tension is found to be accompanied by a progressive fall in intracellular 3′,5′ cyclic AMP and a concomitant rise in 3′,5′ cyclic GMP. These effects are dose related. It is suggested that the ability of adenosine to stimulate 3′,5′ cyclic nucleotide turnover is the result of a fall in intracellular Ca2+, acting via the Ca2+-binding protein modulator, calmodulin. Interestingly, the extent to which the contractile response is depressed is found to be paralleled closely by a quantitatively equivalent reduction in the ratio 3′,5′ cyclic AMP: 3′,5′ cyclic GMP. A possible biochemical basis for the antagonistic regulatory effects of 3′,5′ cyclic AMP and 3′,5′ cyclic GMP on ventricular contractility, implied by these (and other) results, is discussed briefly.
  Journal of Molecular and Cellular Cardiology 04/1980; · 5.17 Impact Factor
• Article: Synthesis, Decomposition, and Vasodilator Action of Some New S-Nitrosated Dipeptides

  Anthony R. Butler, Haitham H. Al-Sa'doni, Ian L. Megson, Frederick W. Flitney
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  ABSTRACT: A number of amino acid methyl esters have been coupled toN-acetylpenicillamine to give a range of sulfur-containing dipeptides. These have been nitrosated to give a family of structurally related NO-donor drugs. The catalytic effect of copper ions upon the release of NO from these compounds is much less than that uponS-nitroso-N-acetylpenicillamine. However, all the nitrosated dipeptides respond in a similar way with little variation in the value ofkCu. On the other hand, the vasodilator action of these compounds and the inhibiting effect of hemoglobin do vary quite considerably within the family. It is suggested that this indicates some tissue penetration by these drugs.
  Nitric Oxide.
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  Article: NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist's perspective

  Anthony R. Butler, Frederick W. Flitney, D.Lyn H. Williams
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  ABSTRACT: The multiplicity of biological functions thus far attributed to NO has led to suggestions that some effects might be mediated by other, related species instead. The radical nature of NO cannot account for its cytotoxicity, but its reaction with Superoxide to form peroxynitite and highly reactive hydroxyl radicals may be important in this context. The ease with which NO can react with and destroy FeS clusters is also an important factor. Nitrosonium and nitroxide ions can be produced in vivo and will react under conditions that are physiologically relevant. Both could, in theory, serve in cell signalling or as cytotoxic agents. More direct experimental evidence for their involvement is needed before we can confidently assign them specific biological roles. In this article, Anthony Butler, Frederick Flitney and Lyn Williams discuss the chemistry of NO and related species.
  Trends in Pharmacological Sciences.