Identification of β adrenoceptors during thymocyte ontogeny in mice

Abstract

Abstract Thymocytes have been studied at various stages during ontogeny in relation to their responsiveness to β adrenoceptor agonists and ability to bind L‐[propyl‐2,3‐ 3 H]dihy‐droalprenolol ([ 3 H]DHA), a specific radioligand of the β adrenoceptor. Specific [ 3 H]DHA binding and the activity of an isoproterenol‐sensitive adenylate cyclase were compared and correlated between (14 to 20‐day) fetal mouse thymocytes and young adult thymocytes. Preliminary experiments show that [ 3 H]DHA binding to thymocytes demonstrated the kinetics, affinity and stereospecificity expected of binding to adenylate cyclase‐coupled β adrenoceptors. Similarly, isoproterenol was shown to selectively increase intracellular adenosine 3′: 5′‐cyclic monophosphate (cAMP) levels and was antagonized by propranolol (a β adrenoceptor antagonist), but not by phentolamine (an a adrenoceptor antagonist), nor by lignocaine (a local anesthetic). The rises in fetal thymocyte cAMP levels found after stimulation with isoproterenol were of greater magnitude than in adult thymocytes. The number of [ 3 H] DHA‐binding sites in both fetal and adult thymocytes was the same (B max = 50 fmol/2 × 10 6 cells). However, the affinity of the binding sites for [ 3 H] DHA was less for the adult cells than the fetal cells (with K D values of 8.0 and 2.2 nM, respectively); this was reflected in the amount of [ 3 H] DHA bound being up to 8 times greater in the embryonic cells.