Developmental enhancement of secretory response to isoproterenol coupled with increases in β-adrenoceptor density and Gs protein function in rat parotid tissues

Abstract

The β-adrenergic agonist, isoproterenol (IPR), stimulated more significantly and sensitively amylase secretion from both the tissues of 7- and 56-day-old rats than a cholinergic agonist, carbachol, at the same concentration. The EC 50 value of amylase secretion with IPR decreased significantly during development but that with carbachol did not change. Estimation by measuring bindings of [ 3H]dihydroalprenolol and [ 3H]quinuclidynylbenzylate indicated the marked increases in the numbers of both β-adrenoceptors and muscarinic receptors in the tissues during development. The affinity of β-adrenoceptors for the agonist was also enhanced during development, but that of muscarinic receptors for the agonist was not. These developmental changes in the number and affinity of β-adrenoceptors and muscarinic receptors paralleled those in amylase secretory response of the tissues to their agonists. The response of adenylate cyclase (AC) of the tissues to 1 μM IPR was steadily enhanced after birth. In contrast, the response of AC to 1 μM forskolin was high until 14 days old, but markedly decreased at 28 days old and thereafter maintained this level. The increase in cholera toxin-catalyzed ADP-ribosylation (AR) of stimulatory GTP binding proteins (Gs proteins) in the tissues was apparent at 14 days old, reaching a maximum at 56 days old and thereafter decreasing with age. On the other hand, pertussis toxin-catalyzed AR of inhibitory GTP binding proteins (Gi proteins) did not change after birth. Thus, the ratio of apparent levels of Gs to Gi proteins increased significantly after birth, reaching a maximum at 56 days old, but decreased rapidly till 84 days old and thereafter maintained this level. These changes in the ratio paralleled those in the response of AC to IPR. These results showed that the rapid and marked increases in the number and affinity of β-adrenoceptors and the ratio of apparent levels of Gs to Gi proteins in rat parotid tissues during development had a key role in the enhancement of the secretory response of the tissues to β-agonists.