Mechanisms underlying the alterations of biosignal transduction and cell response in salivary glands

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The functional alterations of cell surface receptors cause the changes of G protein functions and of cellular responses. In this study, we investigated the mechansims underlying the alterations of cell responses of salivary glands induced by beta agonists, acetylcholine or histamine, and the age-dependent changes in the cell proliferation of the glands of rats treated with beta agonists, and obtained the results as follows.(1) Treatment for 30min of saliary glands with isoproterenol (IPR) or histamine resulted in the desensitization of salivary secretion in response to the agonist. The treatment for less than 10min with IPR caused conversely the supersensitivity of the secretion, but that with histamine did not.(2) The enhancement and the suppresion of Gi protein functions were coupled with the desensitization and the supersensitivity induced by IPR,respectively. But the changes in Gs protein functions were not observed in the tissues caused the desensitization or the supersensitivity. Immunoblot analyzes with AS/7 and RM/1 demonstrated that the levels of Gi2alpha and Gsalpha proteins were not modified by beta_2 agonist- or histamine- treatment.(3) The decrease and the increase in the phosphorylation of Gi2alpha protein coupled with the desensitization and the supersensitivity of amylase secretion by IPR,respectively. Pretreatment of the tissues with okadaic acid at the concentrations to inhibit protein phosphatase2A activity completely blocked the enhancement of Gi2alpha protein function and resulted in the disappearance of the desensitization or in the enhancement of the supersensitivity.(4) The changes in the secretory responses of the glands to beta_2 agonists or acetylcholine after birth paralleled with those in the neurotransmitter receptor and in the function of G proteins.(5) The time required to initiate DNA synthesis in the glands after IPR administration increased significantly with age and the level of DNA synthesis decreased markedly till 16 weeks old.