Coexpression of alpha 1A- and alpha 1B-adrenoceptors in the liver of the rhesus monkey (Macaca mulatta).
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.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F. agarcia@ifcsun1.ifisiol.unam.mx
J A
JA
García-Sáinz
M T
MT
Romero-Avila
C
C
González-Espinosa
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression; D008099:Liver / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin