title: Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists.
abstract: BACKGROUND
  Anti-obesity effects of calcium antagonists such as benidipine and nifedipine have been described in rodent obesity models, but the mode of action of the calcium antagonists as anti-obesity agents has not been established.
  
  
  OBJECTIVE
  To examine whether the anti-obesity effects of calcium antagonists (here benidipine) could be ascribed to a direct stimulation of brown adipose tissue (BAT) thermogenesis.
  
  
  METHODS
  Examination of the ability of benidipine to induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat cells from rats, mice and hamsters--and in intact cold-acclimated rats.
  
  
  RESULTS
  Benidipine itself, or in combination with any dose of noradrenaline (NA), was totally unable to induce or augment thermogenesis in isolated brown-fat cells of any species tested. However, it markedly induced thermogenesis in intact animals (approx 60% increase over resting metabolic rate). This effect could be fully inhibited by propranolol.
  
  
  CONCLUSIONS
  Benidipine is itself without thermogenic effect. The thermogenic response in-vivo (and thus presumably the anti-obesity effect) is probably secondary to a previously described general side-effect of calcium antagonists: a release of NA from sympathetic nerves, here most likely directly from nerves in the BAT. The anti-obesity effect of benedipine is thus probably not due to its calcium channel blocking effect.
  
  
  CONCLUSIONS
  It is probable that the anti-obesity effects of calcium antagonists reported in several models of genetically obese rodents (MSG-obese and agouti mice, SHHF/Mcc-fa(cp) and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To what extent calcium antagonists may induce similar effects in a clinical situation, is currently unknown.
authors: The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Sweden.
authors: J
authors: J
authors: Zhao
authors: V
authors: V
authors: Golozoubova
authors: T
authors: T
authors: Bengtsson
authors: B
authors: B
authors: Cannon
authors: J
authors: J
authors: Nedergaard
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006224:Cricetinae; D004095:Dihydropyridines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine; D011433:Propranolol; D009638:Norepinephrine