Alpha-adrenergic receptor-mediated thermogenesis in brown adipose tissue of rat.
1. The present studies were undertaken to characterize the thermogenic response to the alpha 1-adrenergic agonist phenylephrine, to compare this response with the beta-adrenergic response and to assess the role of brown adipose tissue (BAT). 2. Phenylephrine and the beta 3-adrenergic agonist CGP 12177A each caused similar increases in O2 consumption. No synergism was observed when combining the two drugs. Phenylephrine stimulated O2 consumption via an alpha-adrenergic mechanism, as indicated by effective blockade with phenoxybenzamine, but not propranolol. 3. Further evidence for the alpha-adrenergic mechanism of phenylephrine action was seen in studies with BAT membranes. Phenylephrine did not stimulate adenylyl cyclase and did not potentiate beta-adrenergic stimulation of adenylyl cyclase. 4. Skeletal muscle was not a major site of phenylephrine-stimulated O2 consumption, as the response was not inhibited by a concentration of dantrolene which inhibited cold-induced muscle shivering. 5. Phenylephrine caused an increase in the density of available 3H-GDP binding sites in BAT mitochondria, indicating an activation of BAT thermogenesis in vivo. This increase was equal in magnitude to what we have reported previously for CGP-12177A. No changes were observed in the affinity for 3H-GDP. 6. We concluded that phenylephrine stimulates O2 consumption by an alpha-adrenergic mechanism that involves activation of BAT thermogenesis. It remains to be determined whether the activation of BAT occurs by a direct or indirect mechanism.
Borst
S E
SE
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608-1197, USA.
Oliver
R J
RJ
Sego
R L
RL
Scarpace
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D006153:Guanosine Diphosphate / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D006153:Guanosine Diphosphate; D010656:Phenylephrine; D000262:Adenylyl Cyclases