Desensitization effect of in vivo treatment with metaproterenol on beta1, beta2 and beta3-adrenergic responsiveness in rat adipocytes.
The desensitization process of beta-adrenergic system was assessed by in vivo administration to 7-week old rats of a mixed beta-agonist, metaproterenol (3,5-dehydroxyphenyl-N-isopropyl-amine-beta-ethanol sulphate; T1/2=6 hours), (2 mg/kg/d) in treatments of 12 hours, 2 days and 10 days. The in vitro lipolytic effect of selective beta-adrenergic agonists, dobutamine, salbutamol and BRL 37344, as well as plasma free fatty acid concentrations were measured in treated and control animals given vehicle. Different times of exposure to a beta-agonist induced a loss of responsiveness on lipolytic response mediated by beta1 and beta2-adrenoceptors, as demonstrated by decreased affinity and intrinsic activity (maximal effect) of dobutamine and salbutamol. In contrast, no changes were found in beta3 mediated lipolysis. These observations suggest that beta1, beta2 and beta3-adrenoceptors follow different regulatory patterns. Lack of beta3-adrenoceptor desensitization may have important physiological and therapeutic consequences in the treatment of diseases such as obesity and heart failure.
Portillo
M P
MP
Dep. Nutrition and Food Science, University of Pais Vasco, Vitoria, Spain.
Del Barrio
A S
AS
Garcia-Calonge
M A
MA
Martinez
J A
JA
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004280:Dobutamine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D009921:Metaproterenol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D005230:Fatty Acids, Nonesterified; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D004280:Dobutamine; D009921:Metaproterenol; C057368:BRL 37344; D000420:Albuterol