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Regulation of multiple forms of cyclic nucleotide phosphodiesterase from bovine hypothalamus: New factors modulating enzyme activity

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Abstract

Studies of bovine hypothalamic cyclic nucleotide phosphodiesterase (PDE) indicate the presence of several peaks of PDE activity, distinguishable by DEAE-cellulose column chromatography, displaying different substrate specificities, kinetic behavior, and regulatory properties. Evidence is presented that chromatographically separated forms of PDE activity are subject to control by Ca2+-calmodulin, cyclic nucleotides, limited proteolysis, reagents affecting sulfhydryl groups, and neurohormone “C”—one of several new cardioactive compounds isolated from hypothalamic magnocellular nuclei of animals—in a complex substrate-specific and concentration-dependent manner. Of particular interest is the finding that each of the forms of cGMP PDE, being Ca2+/calmodulin-dependent, possesses sensitivity to activation by cAMP, especially under conditions favoring the oxidation of thiol groups of PDE, resulting in a loss in responsiveness of the enzyme to the activation by calmodulin. This effect appears to be relatively stable but readily reversible by sulfhydryl reducing reagents, which restore both the cGMP PDE sensitivity to competitive inhibition by cAMP and the responsiveness of the enzyme to activation by calmodulin. A reinterpretation of the regulatory properties of multiple forms of PDE is proposed.

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Authors and Affiliations

  1. Institute of Biochemistry, Armenian SSR Academy of Sciences, Sevag str. 5/1, 375044, Yerevan, U.S.S.R.

    A. A. Galoyan (Correspondent-member of Acad. Sci. Arm. S.S.R., Director of the Institute of Biochemistry of Acad. Sci. Arm. S.S.R.) & B. Ya. Gurvitz (Senior research scientist)

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  1. A. A. Galoyan
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  2. B. Ya. Gurvitz
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Special Issue dedicated to Dr. Eugene Kreps.

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Galoyan, A.A., Gurvitz, B.Y. Regulation of multiple forms of cyclic nucleotide phosphodiesterase from bovine hypothalamus: New factors modulating enzyme activity. Neurochem Res 10, 1467–1481 (1985). https://doi.org/10.1007/BF02430598

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