The Mechanism of Changes in Adrenoceptor-Mediated Responses

Abstract

AbstractQuantitative and qualitative changes in adrenoceptors under various conditions were studied by binding experiments. Chronic treatment with reserpine increased the level of α2-adrenoceptors in rat vas deferens and hypoxia increased the level of α1-adrenoceptors in rat cardiomyocytes. Adenosine receptor agonists increased the affinity of the adrenoceptor in rat vas deferens for the agonist with an increase in receptor-media ted responses. Thus two types of changes in receptor binding sites were observed. Next, changes in the GTP-binding (G) protein were studied. Activation of cyclic AMP-dependent protein kinase (PKA) decreased the ADP-ribosylation of Gi (41 K) protein by islet-activating protein (pertussis toxin, IAP). Purified G i protein was phosphorylated by the enzyme. IAP-sensitive G protein-mediated coupling responses such as phosphatidylinositol turnover in differentiated HL-60 cells were also modified under this condition. These results indicated that phosphorylation of G i by PKA caused a qualitative change of Gi. Lithium ions also decreased the ADP-ribosylation of Gi by IAP. Then it determined if the decrease was accompanied with a’dissociation of the subunits of Gi. Phosphorylation of Gi by PKA impaired the dissociation of the subunits of Gi caused by Mg2+ and GTPγS. wheareas lithium ions did not have any effect on their dissociation. Thus some conditions caused a functional change in the so-called “qualitative change” of Gi.