Adrenoceptor of the alpha₂‐subtype mediating inhibition of the human fat cell adenylate cyclase

In an attempt to characterize the adenylate cyclase-coupled alpha-adrenoceptors of human fat cells the effects of various alpha-adrenergic agonists and antagonists were examined in the presence of 0.05 mmol/l of propranolol. The order of agonist potencies with respect to alpha-adrenergic inhibition was (-)-adrenaline greater than alpha-methyl-(-)-noradrenaline greater than (-)-phenylephrine with half-maximal inhibition occurring at 2 mumol/l of (-)-adrenaline and 7 mumol/l of alpha-methyl-(-)-noradrenaline respectively. The inhibition of adenylate cyclase induced by 0.05 mmol/l of (-)-adrenaline was reversed by the alpha-blocking agents yohimbine and prazosin, with the alpha 2-site-directed antagonist yohimbine being more than 100-times more potent than prazosin which is more active at alpha 1-sites. The results show that the cyclase-coupled alpha-adrenoceptors of human fat cells, which probably represent the physiologically relevant target of antilipolytic catecholamine effects, display characteristic features of the alpha 2-adrenoceptor subtype.