Beta-Adrenoceptor agonists and other cAMP elevating agents suppress PAI-1 production of human adipocytes in primary culture.
Recent studies showed that catecholamines contribute to the regulation of plasminogen activator inhibitor-1 (PAI-1) expression, at least in endothelial cells. Aim of this study was to examine the role of catecholamines on PAI-1 production by human adipocytes and, in particular, to clarify which adrenoceptor (AR) subtypes are involved. Addition of the unselective AR agonist isoproterenol led to a dose- and time-dependent suppression of PAI-1 mRNA and protein release in adipocytes from the subcutaneous and omental depot of obese subjects. A similar degree of suppression was observed in subcutaneous mammary adipocytes of lean women. This effect was mainly mediated via the beta2-adrenoceptor according to experiments using selective agonists. Moreover, addition of cAMP-elevating agents such as dibutyryl-cAMP, forskolin and the phosphodiesterase inhibitors isobutyl-methylxanthine and milrinone resulted in a reduction of PAI-1 of varying degrees. In conclusion, the results of this study support the assumption that catecholamines are able to down-regulate PAI-1 expression and secretion in human adipocytes via beta-adrenergic receptors.
Gottschling-Zeller
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German Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department.
Aprath
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I
Skurk
T
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Hauner
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001940:Breast; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D020105:Milrinone / Q000494:pharmacology; D009852:Omentum; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D020105:Milrinone; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine