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Characterization of rat liver β‐adrenoceptors during perinatal development as determined by [ 125 I]‐iodopindolol radioligand binding assays
Author(s) -
Snell Keith,
Evans Carole A.
Publication year - 1988
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.1476-5381.1988.tb11467.x
Subject(s) - atenolol , radioligand , dissociation constant , isoprenaline , radioligand assay , endocrinology , medicine , binding site , chemistry , population , receptor , biology , biochemistry , blood pressure , stimulation , environmental health
1 The subtype specificity of β‐adrenoceptors in foetal (20 days post coitum) rat liver membrane preparations has been determined by use of [ 125 I]‐iodopindolol binding assays and the characteristics of radioligand binding have been resolved. 2 The kinetics of radioligand association and dissociation (in the presence of 5 × 10 −4 m isoprenaline) showed an association rate constant of 1.5 × 10 7 m −1 s −1 and dissociation rate constant of 9.1 × 10 −4 s −1 , corresponding to a dissociation constant for [ 125 I]‐iodopindolol of 60.7 p m . A similar dissociation constant (75 p m ) was determined by saturation binding assays. 3 The rank order of potency for displacement of [ 125 I]‐iodopindolol binding was consistent with binding to a predominantly β 2 ‐adrenoceptor population (i.e. ICI 118551 > isoprenaline > adrenaline > noradrenaline > atenolol). Computer analysis of displacement curves in the presence of a β 1 ‐subtype selective agent (atenolol) or a β 2 ‐subtype selective agent (ICI 118551) revealed the presence of β 2− and β 1 ‐adrenoceptor subtypes in a ratio of about 80: 20%. 4 Saturation binding assays by use of [ 125 I]‐iodopindolol were carried out at different perinatal ages to determine total β‐adrenoceptor concentrations and β 2 ‐subtype (in the presence of 5 × 10‐ 7 m atenolol) adrenoceptor concentrations. Competition binding assays with atenolol confirmed that at all ages apparent β 2 ‐adrenoceptor binding accounted for 84–95% of the total β‐adrenoceptor binding. The total β ‐ and β 2 ‐adrenoceptor binding capacity increased by 2.3 fold from 20 days post coitum to birth, and then decreased postnatally at 1 and 2 days post partum. The dissociation constant for [ 125 I]‐iodopindolol binding did not show any change with age. 5 The change in β 2 ‐adrenoceptor concentration with age is discussed in relation to the changing β‐adrenoceptor‐mediated responsiveness of glucose production by rat liver during perinatal development.