Effects of acute and chronic ethanol administration on the response of mouse adipose tissue hormone-sensitive lipase to alpha(2)-adrenoceptor activation bu UK 14304.
Untreated (control) obese CBA mice had lower hormone-sensitive lipase (HSL) activity and cAMP levels in brown adipose tissue than normal lean mice, but white adipose tissue HSL activity and cAMP were similar in obese and lean mice. In the obese mice, chronic ethanol treatment increased HSL activity and cAMP levels in both brown and white adipose tissue to above the levels in lean mice. In the lean mice, chronic ethanol only stimulated white adipose tissue. UK 14304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline: 2 mg/kg] inhibited HSL activity in both brown and white adipose tissues in lean mice, but a higher dose (3 mg/kg) was required to produce the same inhibition in obese mice. After chronic ethanol adipose tissues were more sensitive to UK 14304; only half the dose being required to produce the same level of lipase inhibition. We propose that, although chronic ethanol consumption increases cAMP levels in adipose tissue, particularly in obese mice, it also sensitizes the tissues to alpha(2)-adrenoceptor stimulation. These effects may explain the increased sympathetic nervous system activity observed in alcohol withdrawal.
Shih
M F
MF
Department of Pharmacology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
Taberner
P V
PV
D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000096:biosynthesis; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009765:Obesity / Q000201:enzymology / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D002492:Central Nervous System Depressants; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000431:Ethanol; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP; D002787:Sterol Esterase