Discrepancies in lipolytic activities induced by beta-adrenoceptor agonists in human and rat adipocytes.
A number of catecholamine and non-catecholamine beta-adrenoceptor agonists, including the lipolytically selective compound BRL 37344, were compared for lipolytic activity on human and rat adipocytes. On rat adipocytes, all compounds were full agonists, BRL 37344 being the most potent. On human adipocytes, only the catecholamines were full beta-adrenoceptor agonists. The other compounds were partial agonists, with intrinsic activities declining in the order fenoterol greater than salbutamol greater than clenbuterol greater than BRL 37344. This was the case with FFA- as well as with glycerol-production. Addition of 20 microM phentolamine did not enhance BRL 37344 activity. The isoprenaline- and BRL 37344-induced lipolysis on rat white adipocytes was stereoselectively antagonized by enantiomers of alprenolol, with atypical low potencies and stereoselectivity. It was concluded that (1) human and rat adipocyte beta-adrenoceptors mediating lipolysis are not essentially different, (2) partial agonism in human adipocytes is not explained by enhanced re-esterification and (3) BRL 37344 selectively stimulates rat adipocyte lipolysis.
Hollenga
C
C
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
Haas
M
M
Deinum
J T
JT
Zaagsma
J
J
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000368:Aged; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005990:Glycerol / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004983:Ethanolamines; D005230:Fatty Acids, Nonesterified; C057368:BRL 37344; D000526:Alprenolol; D007545:Isoproterenol; D005990:Glycerol