Coexpression of alpha 1A- and alpha 1B-adrenoceptors in the liver of the rhesus monkey (Macaca mulatta)

Eur J Pharmacol. 1996 Sep 12;311(2-3):277-83. doi: 10.1016/0014-2999(96)00433-5.

Abstract

The alpha 1-adrenoceptors present in the liver of rhesus monkeys was characterized using [3H]prazosin. This radioligand binds to monkey liver membranes with high affinity (KD 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 alpha 1A-adrenoceptor-selective agonists): oximetazoline > or = 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-metoxybenzen esulfonamide HCl (tamsulosin) > or = 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane (WB4101) > or = prazosin > or = (+)-niguldipine > 5-methylurapidil = benoxathian > phentolamine > 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]deca ne-7,9- dione dihydrochloride (BMY 7378); (b) for the other sites (low affinity for the alpha 1A-adrenoceptor-selective antagonists): prazosin > tamsulosin > phentolamine = WB4101 > (+)-niguldipine > or = 5-methyl-urapidil = benoxathian > BMY 7378. These data strongly suggest that Macaca mulatta liver cells coexpress alpha 1A- and alpha 1B-adrenoceptors. Expression of the mRNA for these receptors was confirmed by reverse transcriptase-polymerase chain reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / metabolism
  • Adrenergic alpha-Antagonists / metabolism*
  • Animals
  • Binding Sites
  • Binding, Competitive
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Female
  • Gene Expression
  • Liver / metabolism*
  • Macaca mulatta
  • Male
  • Prazosin / metabolism
  • Radioligand Assay
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-1
  • Prazosin