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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Cedric Moro, Jean Galitzky, Coralie Sengenes, François Crampes, Max Lafontan and Michel Berlan
Journal of Pharmacology and Experimental Therapeutics March 2004, 308 (3) 984-992; DOI: https://doi.org/10.1124/jpet.103.060913
Cedric Moro
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Jean Galitzky
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Coralie Sengenes
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François Crampes
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Max Lafontan
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Michel Berlan
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Abstract

A lipolytic pathway involving natriuretic peptides has recently been discovered in human fat cells. Its functional characteristics and the interactions of the atrial natriuretic peptide (ANP)-induced effects with adrenergic and insulin pathways were studied. Characterization of the action of ANP antagonists, i.e., A71915, anantin, S-28-Y (Ser-28-Tyr, a synthesized peptide), and HS-142-1 (a microbial polysaccharide), was performed. Lipolytic assays and intracellular cGMP and cAMP determinations were performed on isolated fat cells. Cell membranes were used for binding studies. At low concentrations ANP and isoproterenol [β-adrenergic receptor (β-AR) agonist] exerted additive lipolytic effects. The α2-AR pathway did not interfere with that of ANP. Lipolytic effects of ANP were unaltered by a 2-h pretreatment of fat cells with insulin, whereas β-AR-induced lipolysis was reduced. Homologous desensitization occurred for ANP-dependent lipolytic pathways. Dendroapsis natriuretic peptide exhibited a similar maximal effect but a 10-fold higher lipolytic potency than ANP and mini-ANP (the shortest form of ANP). The antagonist A71915 exhibited competitive antagonistic properties with a pA2 value of 7.51. Anantin displayed noncompetitive antagonism and exerted an inhibitory action on basal and β-adrenergic receptor-induced lipolytic response. S-28-Y exhibited antagonist potencies toward ANP-induced lipolysis and behaved as a partial lipolytic agonist with a lower pD2 value (7.4 ± 0.2) than ANP (9.4 ± 0.3). HS-142-1 exerted the weakest antagonistic effects. The results demonstrate that ANP-dependent effects do not interfere with β- and α2-adrenergic pathways in human fat cells. They are unaffected by insulin pretreatments of fat cells but undergo desensitization. In the search of potent and specific natriuretic peptide receptor-A antagonist, in the human fat cell, A71915 was the only reliable one found.

Footnotes

  • DOI: 10.1124/jpet.103.060913.

  • ABBREVIATIONS: ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; NP, natriuretic peptide; NPR, natriuretic peptide receptor; AR, adrenergic receptor; DNP, dendroapsis natriuretic peptide; KRBA, Krebs Ringer bicarbonate buffer containing bovine serum albumin; S-28-Y, Ser-28-Tyr; HS-142-1, polysaccharide isolated from culture broth of Aureobasidium sp.

    • Received October 3, 2003.
    • Accepted November 17, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 308 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 308, Issue 3
1 Mar 2004
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Cedric Moro, Jean Galitzky, Coralie Sengenes, François Crampes, Max Lafontan and Michel Berlan
Journal of Pharmacology and Experimental Therapeutics March 1, 2004, 308 (3) 984-992; DOI: https://doi.org/10.1124/jpet.103.060913

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells

Cedric Moro, Jean Galitzky, Coralie Sengenes, François Crampes, Max Lafontan and Michel Berlan
Journal of Pharmacology and Experimental Therapeutics March 1, 2004, 308 (3) 984-992; DOI: https://doi.org/10.1124/jpet.103.060913
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