DEVELOPMENTAL ENHANCEMENT OF SECRETORY RESPONSE TO ISOPROTERENOL COUPLED WITH INCREASES IN BETA-ADRENOCEPTOR DENSITY AND GS PROTEIN FUNCTION IN RAT PAROTID TISSUES

The beta-adrenergic agonist, isoproterenol (IPR), stimulated more sign ificantly and sensitively amylase secretion from both the tissues of 7 - and 56-day-old rats than a cholinergic agonist, carbachol, at the sa me concentration. The EC50 value of amylase secretion with IPR decreas ed significantly during development but that with carbachol did not ch ange. Estimation by measuring bindings of [H-3]dihydroalprenolol and [ H-3]quinuclidynylbenzylate indicated the marked increases in the numbe rs of both beta-adrenoceptors and muscarinic receptors in the tissues during development. The affinity of beta-adrenoceptors for the agonist was also enhanced during development, but that of muscarinic receptor s for the agonist was not. These developmental changes in the number a nd affinity of beta-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 mu M IPR wa s steadily enhanced after birth. In contrast, the response of AC to 1 mu M forskolin was high until 14 days old, but markedly decreased at 2 8 days old and thereafter maintained this level. The increase in chole ra toxin-catalyzed ADP-ribosylation (AR) of stimulatory GTP binding pr oteins (Gs proteins) in the tissues was apparent at 14 days old, reach ing a maximum at 56 days old and thereafter decreasing with age. On th e other hand, pertussis toxin-catalyzed AR of inhibitory GTP binding p roteins (Gi proteins) did not change after birth. Thus, the ratio of a pparent levels of Gs to Gi proteins increased significantly after birt h, reaching a maximum at 56 days old, but decreased rapidly till 84 da ys old and thereafter maintained this level. These changes in the rati o paralleled those in the response of AC to IPR. These results showed that the rapid and marked increases in the number and affinity of beta -adrenoceptors and the ratio of apparent levels of Gs to Gi proteins i n rat parotid tissues during development had a key role in the enhance ment of the secretory response of the tissues to beta-agonists. (C) 19 98 Elsevier Science Ireland Ltd. All rights reserved.