Alpha-2 adrenoceptors in lipolysis: alpha 2 antagonists and lipid-mobilizing strategies.
The lipid-mobilizing and thermogenic effects of several alpha 2 antagonists were explored. Studies were undertaken in humans and in the dog, which possess fat-cell alpha 2-adrenergic receptors (alpha 2-AR) and beta-adrenergic receptors (beta-AR) that are very similar. Yohimbine (alpha 2-AR antagonist) was used in humans whereas other recent alpha 2 antagonists were used in dogs. Oral yohimbine (0.2 mg/kg) promoted a lasting increment of plasma nonesterified fatty acids (NEFAs) and noradrenaline concentrations without significant action on cardiovascular parameters or insulin secretion. In dogs, a direct correlation between the variations of plasma NEFA and noradrenaline concentrations induced by alpha 2 antagonists (1.2 mmol/kg iv) was observed; a result supporting the relationship between lipolysis and the pharmacologic activation of the sympathetic nervous system. Cardiovascular effects were almost absent whereas a long-lasting thermogenic effect was observed. The lipid-mobilizing effect of alpha 2 antagonists is mainly attributable to the increase in synaptic noradrenaline. The potential interest of alpha 2 antagonists in diet therapy is discussed.
Lafontan
M
M
INSERM, Unité 317, Institut Louis Bugnard, Université Paul Sabatier, Toulouse, France.
Berlan
M
M
Galitzky
J
J
Montastruc
J L
JL
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D005230:Fatty Acids, Nonesterified; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine