Castronuovo G, Lippe C, Bellantuono V, Calzaretti G, Ardizzone C
Institute of General Physiology, University of Bari, Italy.
Arch Physiol Biochem. 1996;104(2):142-7. doi: 10.1076/apab.104.2.142.12892.
Calcitonin gene-related peptide (CGRP) added to the internal fluid bathing the isolated skin of Rana esculenta strongly stimulates the active sodium absorption. This action is dose-dependent, the dose eliciting the maximal effect being 2 . 10(-7) M; alpha and beta CGRP exhibit the same potency. The CGRP action on sodium transport is mainly due to its interaction with CGRP1 receptors, since it is inhibited by CGRP8-37, its specific antagonist. The second messengers probably involved in the action of CGRP are cAMP and Ca+2, since this action is reduced by SQ22536 and W7, which are inhibitors of adenyl cyclase and calmodulin respectively. On the contrary, inhibitors of protein kinase C (1-O-hexadecyl-2-O-methyl-sn-glycerol) and nitric oxide synthase (L-NAME) do not modify the action on sodium transport. ETYA, an inhibitor of all the metabolic pathways of arachidonic acid, decreases the CGRP action by 38%. In order to search for the arachidonic acid metabolites involved in the CGRP action, the effect of the following inhibitors was tested: aspirin and naproxen (for cyclooxygenases), NDGA (for cyclooxygenases), NDGA (for lipoxygenases) clotrimazole (for epoxygenases). None of these substances is able to inhibit the CGRP action on sodium transport. Moreover, adding arachidonic acid inhibits the CGRP action, but this effect was also obtained by another unsaturated fatty acid, oleic acid. Since unsaturated fatty acids are able to inhibit the protein kinase A, these results indirectly support the role of cAMP as a second messenger of the CGRP action on sodium transport.
降钙素基因相关肽（CGRP）添加到离体食用蛙皮肤的内部灌流液中，可强烈刺激钠的主动吸收。此作用呈剂量依赖性，产生最大效应的剂量为2×10⁻⁷M；α型和β型CGRP具有相同的效力。CGRP对钠转运的作用主要归因于其与CGRP1受体的相互作用，因为其特异性拮抗剂CGRP8 - 37可抑制该作用。可能参与CGRP作用的第二信使是cAMP和Ca²⁺，因为分别作为腺苷酸环化酶抑制剂和钙调蛋白抑制剂的SQ22536和W7可减弱此作用。相反，蛋白激酶C抑制剂（1 - O - 十六烷基 - 2 - O - 甲基 - sn - 甘油）和一氧化氮合酶抑制剂（L - NAME）并不改变对钠转运的作用。花生四烯酸所有代谢途径的抑制剂ETYA可使CGRP的作用降低38%。为了探寻参与CGRP作用的花生四烯酸代谢产物，测试了以下抑制剂的作用：阿司匹林和萘普生（针对环氧化酶）、去甲二氢愈创木酸（针对环氧化酶）、去甲二氢愈创木酸（针对脂氧化酶）、克霉唑（针对环氧合酶）。这些物质均不能抑制CGRP对钠转运的作用。此外，添加花生四烯酸可抑制CGRP的作用，但另一种不饱和脂肪酸油酸也能产生此效应。由于不饱和脂肪酸能够抑制蛋白激酶A，这些结果间接支持了cAMP作为CGRP对钠转运作用的第二信使的作用。
