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Effects of phorbol esters, A23187 and vasopressin on oleate metabolism in isolated rat hepatocytes

  • Published:
Lipids

Abstract

Studies were conducted to compare the metabolic effects of vasopressin, 4β-phorbol-12-myristate-13-acetate (PMA) and A23187 on ketogenesis and oleate metabolism in isolated hepatocytes from fed rats. Vasopressin inhibited the formation of acid-soluble products from [1-14C]oleate (0.25 mM, 0.5 mM and 1 mM), the inhibition being most marked at low (0.25 mM) concentration of oleate. Conversion of [1-14C]oleate into14CO2 and esterified products was stimulated by vasopressin. The stimulatory effect of this hormone on14CO2 production was most marked at high (1 mM) concentration of oleate, whereas that on [1-14C]-oleate esterification was most marked at low (0.25 mM) concentration of oleate. These vasopressin actions were abolished when hepatocytes were incubated in the absence of calcium in the medium. Our results strongly suggest that both increase in esterification and increase in oxidation to CO2 contribute to the anti-ketogenic action of vasopressin when oleate is added as substrate, although the relative extent of their contribution varies according to the oleate concentration. The anti-ketogenic action of vasopressin was mimicked by PMA but not by A23187. PMA also caused a stimulation of [1-14C]oleate esterification although the effect was diminished at 1 mM [1-14C]oleate. A23187 failed to affect [1-14C]oleate esterification. The metabolic effects of PMA were elicited in the absence of extracellular calcium, too. Conversion of [1-14C]oleate into14CO2 was only slightly increased by both PMA and A23187 when 1 mM [1-14C]oleate was added as substrate. The marked stimulatory effect of vasopressin on14CO2 production from [1-14C]oleate was not reproduced even by the combination of PMA and A23187. The possible involvement of protein kinase C and calcium mobilization in the regulation of oleate metabolism is discussed.

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Abbreviations

EGTA:

ethyleneglycol-bis-(β-aminoethyl ether)N,N′-tetraacetic acid

PMA:

4β-phorbol-12-myristate-13-acetate

4α-PDD:

4α-phorbol-12,13-didecanoate

4β-PDD:

4β-phorbol-12,13-didecanoate

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Authors and Affiliations

  1. Department of Pharmacology, Fujita-Gakuen Health University, School of Medicine, Kutsukake-cho, Toyoake, 470-11, Aichi, Japan

    Takahide Nomura, Masakatsu Tachibana, Hiroko Nomura, Masaru Chihara & Yasumichi Hagino

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  1. Takahide Nomura
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  2. Masakatsu Tachibana
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  3. Hiroko Nomura
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  4. Masaru Chihara
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  5. Yasumichi Hagino
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Nomura, T., Tachibana, M., Nomura, H. et al. Effects of phorbol esters, A23187 and vasopressin on oleate metabolism in isolated rat hepatocytes. Lipids 22, 474–479 (1987). https://doi.org/10.1007/BF02540362

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  • DOI: https://doi.org/10.1007/BF02540362

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