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Characterization of rat liver β‐adrenoceptors during perinatal development as determined by [125I]‐iodopindolol radioligand binding assays

1 The subtype specificity of β‐adrenoceptors in foetal (20 days post coitum) rat liver membrane preparations has been determined by use of [125I]‐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 × 107 m−1 s−1 and dissociation rate constant of 9.1 × 10−4 s−1, corresponding to a dissociation constant for [125I]‐iodopindolol of 60.7 pm. A similar dissociation constant (75 pm) was determined by saturation binding assays. 3 The rank order of potency for displacement of [125I]‐iodopindolol binding was consistent with binding to a predominantly β2‐adrenoceptor population (i.e. ICI 118551 > isoprenaline > adrenaline > noradrenaline > atenolol). Computer analysis of displacement curves in the presence of a β1‐subtype selective agent (atenolol) or a β2‐subtype selective agent (ICI 118551) revealed the presence of β2− and β1‐adrenoceptor subtypes in a ratio of about 80: 20%. 4 Saturation binding assays by use of [125I]‐iodopindolol were carried out at different perinatal ages to determine total β‐adrenoceptor concentrations and β2‐subtype (in the presence of 5 × 10‐7 m atenolol) adrenoceptor concentrations. Competition binding assays with atenolol confirmed that at all ages apparent β2‐adrenoceptor binding accounted for 84–95% of the total β‐adrenoceptor binding. The total β‐ and β2‐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 [125I]‐iodopindolol binding did not show any change with age. 5 The change in β2‐adrenoceptor concentration with age is discussed in relation to the changing β‐adrenoceptor‐mediated responsiveness of glucose production by rat liver during perinatal development.