Coexpression of α1A- and α1B-adrenoceptors in the liver of the rhesus monkey ( Macaca mulatta)

Abstract

The α 1-adrenoceptors present in the liver of rhesus monkeys was characterized using [ 3H]prazosin. This radioligand binds to monkey liver membranes with high affinity ( K D 0.33 nM) to a moderately abundant number of sites (97 fmol/mg of protein). These sites were characterized pharmacologically, by binding competition, observing two affinities for most ligands. The order of potency for agonists was: (a) for the high affinity sites: oximetazoline > epinephrine = norepinephrine > methoxamine; and (b) for the other sites (low affinity for the α 1A-adrenoceptor-selective agonists): oximetazoline ≥ epinephrine = norepinephrine ⪢ methoxamine. For antagonists the orders of potency were: (a) for the high affinity sites: R-(−)-5[2-[[2-(ethoxyphenoxy)ethyl]amino]propyl]-2-metoxybenzenesulfonamide HCl (tamsulosin) ≥ 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane (WB4101) ≥ prazosin ≥ (+)- niguldipine > 5-methylurapidil = benoxathian > phentolamine > 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione dihydrochloride (BMY 7378); (b) for the other sites (low affinity for the α 1A-adrenoceptor-selective antagonists): prazosin > tamsulosin > phentolamine = WB4101 > (+)-niguldipine ≥ 5-methyl-urapidil = benoxathian > BMY 7378. These data strongly suggest that Macaca mulatta liver cells coexpress α 1A- and α 1B-adrenoceptors. Expression of the mRNA for these receptors was confirmed by reverse transcriptase-polymerase chain reactions.