Esteves R Z, van Sande J, Dumont J E
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Mol Cell Endocrinol. 1992 Dec;90(1):R1-3. doi: 10.1016/0303-7207(92)90115-m.
It is now well established that agonist activation of the PIP2/calcium cascade in the thyroid results in the enhancement of cGMP accumulation presumably by activation of the soluble guanylate cyclase. In many tissues the physiological signal controlling soluble guanylate cyclase is nitric oxide (NO) and its synthesis from arginine is controlled by the intracellular Ca2+. In this report we show results that suggest that NO may be the intermediate of the cGMP response to the activation of the PIP2/calcium cascade. In dog thyroid slices, incubation with carbamylcholine or A23187 increases significantly free intracellular Ca2+ levels and the cGMP content of the slices. NG-Monomethyl-L-arginine (NMMA), a competitive inhibitor of arginine for nitric oxide synthase, inhibited these cGMP responses but not the action of sodium nitroprusside which activates soluble guanylate cyclase directly. The inhibition was relieved by arginine. Methylene blue, which blocks the activation of soluble guanylate cyclase by NO, also decreased the three stimulatory effects. NMMA and methylene blue also decreased the basal levels of cGMP. NO may therefore be an important autocrine and paracrine factor in thyroid.
现已充分证实，甲状腺中PIP2/钙级联的激动剂激活会导致cGMP积累增加，这可能是通过激活可溶性鸟苷酸环化酶实现的。在许多组织中，控制可溶性鸟苷酸环化酶的生理信号是一氧化氮（NO），其从精氨酸合成受细胞内Ca2+控制。在本报告中，我们展示的结果表明，NO可能是对PIP2/钙级联激活产生cGMP反应的中间体。在犬甲状腺切片中，用氨甲酰胆碱或A23187孵育可显著提高细胞内游离Ca2+水平和切片的cGMP含量。NG-单甲基-L-精氨酸（NMMA）是精氨酸对一氧化氮合酶的竞争性抑制剂，它抑制了这些cGMP反应，但不抑制直接激活可溶性鸟苷酸环化酶的硝普钠的作用。精氨酸可解除这种抑制。亚甲蓝可阻断NO对可溶性鸟苷酸环化酶的激活，它也降低了这三种刺激作用。NMMA和亚甲蓝还降低了cGMP的基础水平。因此，NO可能是甲状腺中一种重要的自分泌和旁分泌因子。
