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

细胞表面受体功能的改变导致G蛋白功能和细胞反应的改变。在本研究中，我们研究了β激动剂、乙酰胆碱或组胺引起唾液腺细胞反应改变的机制，以及用β激动剂处理大鼠唾液腺细胞增殖的年龄依赖性变化，结果如下：(1)用异丙肾上腺素(IPR)或组胺处理唾液腺30min，唾液分泌物对激动剂的反应减敏。反之，IPR作用10min可引起细胞分泌的超敏反应，而组胺处理则无此作用。(2)IPR对Gi蛋白功能的增强和抑制分别与IPR的脱敏和超敏作用相耦合。但在脱敏或超敏的组织中未观察到Gs蛋白功能的变化。AS/7和RM/1免疫印迹分析表明，β_2激动剂或组胺处理不改变Gi2pha和Gsalpha蛋白的水平。(3)Gi2pha蛋白磷酸化水平的降低和升高分别伴随着IPR对淀粉酶分泌的脱敏和超敏。用冈田酸抑制蛋白磷酸酶2A活性的浓度可完全阻断Gi2α蛋白功能的增强，导致脱敏作用消失或超敏增强。(4)腺体对β_2激动剂或乙酰胆碱的分泌反应在出生后的变化与神经递质受体和G蛋白的功能变化相一致。(5)IPR后腺体启动DNA合成所需的时间随着年龄的增加而显著增加，DNA合成水平在16周龄前显著下降。

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.