Al teration of GTP binding proteins coupled with secretory response in rat submandibular tissues

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Brief exposure of the tissues to 10muM isoproterenol (IPR) resulted in reduced stimulation of mucin secretion in response to IPR during further incubation coupled with the decrease in the number of beta-adrenoceptors and in the affinity of them for beta-agonist. Treatment of the tissues with IPR caused a 30% decrease in IPR-stimulated adenylate cyclase activity and a 25% increase in the GTP binding capacity of inhibitory GTP binding proteins (Gi proteins). This IPR-treatment triggered a 60% increase in the ability of pertussis toxin (IAP) to catalyze ADP-ribosylation of Gi proteins in the tissue membrane Enhanced function of stimulatory GTP binding proteins (Gs proteins) was observed only during the first incubation of the tissues with IPR.The IAP-catalyzed ADP-ribosylation of Gi proteins in the tissues treated with IPR was decreased by prior treatment with cyclic AMP-dependent protein kinase, but was increased markedly by prior treatment with alkaline phosphatase. The IPR-induced desensitization of j4399 protein secretion and increase in the IAP-catalyzed ADP-ribosylation of Gi proteins were not abserved in the tissues pre-treated with 0.25muM okadaic acid. We also found that GTP binding proteins (G proteins) of molecular weight exists in secretory granule membranes and botulinum toxin has an ability specifically to catalyze ADP-rebosylation of this protein. Release of amylase from the granules was stimulated by ATP or GTPgammaS in the presence of Mg^<2+>. The conformational change in the granules was also caused by these agents, suggesting an importance of the protein in exocytosis.These results suggest that enzymatic modification of the phosphorylation of Gi proteins is important in the regulation of cell response to subsequent stimulation by adrenergic beta-agonists.