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Functional evidence that α2A-adrenoceptors are responsible for antilipolysis in human abdominal fat cells

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Abstract

The effects of α2-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various α-adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA2-values): CH-38083 (7.69 and 7.48) ≅ idazoxan (7.5 and 7.41) > BRL 44408 (7.23 and 7.19) ≅ WB 4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective α2-adrenoceptor antagonists and BRL44408, a selective a2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective α2B-adrenoceptor antagonist failed to affect it. In addition since the α2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (a2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the a2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between α2A- and β-adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis.

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Authors and Affiliations

  1. Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, H-1450, Budapest, Hungary

    Gábor Tarkovács, Corrado Blandizzi & E. Sylvester Vizi

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  1. Gábor Tarkovács
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  2. Corrado Blandizzi
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  3. E. Sylvester Vizi
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On leave from Institute of Medical Pharmacology, University of Pisa, Via Roma 55, I-5626 Pisa, Italy

Correspondence to: E. S. Vizi at the above address

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Tarkovács, G., Blandizzi, C. & Vizi, E.S. Functional evidence that α2A-adrenoceptors are responsible for antilipolysis in human abdominal fat cells. Naunyn-Schmiedeberg's Arch Pharmacol 349, 34–41 (1994). https://doi.org/10.1007/BF00178203

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  • DOI: https://doi.org/10.1007/BF00178203

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