Premium
Two distinct α 1 ‐adrenoceptor subtypes in rabbit liver:a binding study
Author(s) -
Ohmura Tsuyoshi,
Muramatsu Ikunobu
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17212.x
Subject(s) - prazosin , radioligand , population , binding site , chemistry , radioligand assay , stereochemistry , biochemistry , receptor , antagonist , medicine , environmental health
1 . The characteristics of α 1 ‐adrenoceptor subtypes present on rabbit liver membranes were determined by radioligand binding and compared with the characteristics of binding in rat liver. 2 . In saturation experiments using rabbit liver, [ 3 H]‐prazosin bound to two distinct affinity sites ( pK D = 10.3±0.19 and 8.13±0.17, B max = 11.6 ± 3.3 and 657.8± 198.0 fmol mg −1 protein, respectively). In studies using rat liver, [ 3 H]‐prazosin bound to a single affinity site ( pK D = 9.98 ±0.27, B max = 190.5 ±38.5 fmol mg −1 protein). 3 . In competition experiments, unlabelled prazosin displaced biphasically the binding of 200 pM [ 3 H]‐prazosin to the rabbit liver; the resulting two pK I values (9.85 ±0.08 and 8.01 ±0.09) were consistent with the affinity constants obtained in the saturation experiments. Two sites were also recognized by doxazosin ( pK I 9.73±0.78 and 8.12±0.34), 2‐(2,6‐dimethoxy phenoxyethyl)‐aminomethyl‐1,4‐benzo‐dioxane (WB4101) pK I (9.74 ±0.32 and 7.57 ±0.34) and 5‐methylurapidil ( pK I 8.69 ±0.27 and 6.75 ±0.35), and the population of low affinity sites for the three antagonists was approximately 70%. Two distinct affinity constants ( pK I 8.55 ±0.09 and 7.90 ±0.09) were also calculated for α‐ethyl‐3,4,5‐trimethoxy‐α‐(3‐((2‐(2‐methoxyphenoxy) ethyl)‐amino)‐propyl)‐benzeneacetonitrile fumarate (HV723). 4 . By contrast, [ 3 H]‐prazosin binding sites of rat liver membranes were detected as a single population with a high affinity for prazosin ( pK I 10.01 ±0.08), and doxazosin ( pK I 9.67 ±0.20) but with a low affinity for WB4101 ( pK I 8.25 ±0.09), 5‐methylurapidil ( pK I 7.22 ±0.01) and HV723 ( pK I 8.88 ±0.05). 5 . These results indicate the presence of two distinct α 1 ‐adrenoceptor subtypes in the rabbit liver, but only a single site in rat liver. The pharmacological characteristics of prazosin‐high and ‐low sites in rabbit liver suggest identity with α 1A and putative α 1L subtypes, respectively. The site in rat liver is of the α 1B subtype.