Inhibition of lipolysis in hamster adipocytes with selective alpha-adrenergic stimuli. Functional characterization of the alpha-receptor.
This communication shows the relative potencies of the alpha-agonists clonidine, methoxamine, methyl norepinephrine and phenylephrine in producing inhibition of lipolysis. At cell densities greater than 15 mg cell/ml lipolysis activated by either 1-methyl-3-isobutyl xanthine or adenosine deaminase was inhibited by alpha-adrenergic stimuli with a rank order of potency of clonidine greater than methoxamine greater than methyl norepinephrine; phenylephrine produced a further stimulation of lipolysis. At the same cell density isoproterenol-accelerated lipolysis was inhibited by alpha-adrenergic stimuli with a rank order of potency of phenylephrine greater than methoxamine greater than clonidine greater than methyl norepinephrine. When the density of fat cells was reduced to less than 5 mg/ml, clonidine was a more effective inhibitor of isoproterenol-activated lipolysis thatn phenylephrine. Lipolysis that was activated by dibutyryl cyclic AMP, ACTH or cholera enterotoxin was not reduced by any alpha-adrenergic agent. Under conditions when clonidine failed to inhibit catecholamine-activated lipolysis (i.e., at cell densities greater than 15 mg/ml), it failed to antagonize the antilipolytic activity of phenylephrine. The antilipolytic activities of clonidine and phenylephrine were most effectively antagonized by the blocking drugs phentolamine and yohimbine; in contrast, phenoxybenzamine and prazosin were less effective blockers. These data indicate that the alpha-adrenergic receptor on hamster fat cells is similar to presynaptic alpha-adrenergic receptors. The data further suggest the possibility that phenylephrine may exert its action through a separate alpha-adrenergic receptor mechanism.
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D006224:Cricetinae; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008647:Mesocricetus; D008729:Methoxamine / Q000494:pharmacology*; D008771:Nordefrin / Q000494:pharmacology*; D009638:Norepinephrine / Q000031:analogs & derivatives*; D010656:Phenylephrine / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003994:Bucladesine; D008729:Methoxamine; D007545:Isoproterenol; D003000:Clonidine; D008771:Nordefrin; D009638:Norepinephrine