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EFFECTS OF ADRENOMEDULLIN AND PROADRENOMEDULLIN N-TERMINAL 20 PEPTIDE ON RAT ZONA GLOMERULOSA

机译:肾上腺髓质素和前肾上腺素N端20肽对大鼠结扎性肾小球粘膜的影响

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Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) derive from a 185-amino acid prohormone, called preproadrenomedullin, which is highly expressed in rat adrenal medulla. ADM and PAMP did not affect either basal or ACTH-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells. In contrast, both peptides markedly suppressed angiotensin-II-stimulated aldosterone production, PAMP being much more effective than ADM (minimal effective concentration, 10(-10) M versus 10(-8) M. IC50, 2.0 +/- 0.17 x 10(-9) M versus 3.1 +/- 0.22 x 10(-8) M; P<0.01. Maximum inhibition, 80% versus 43%, respectively). The inhibitory effect of 10(-7) M ADM was completely reversed by the competitive antagonist of type 1 calcitonin gene-related peptide (CGRP) receptors CGRP(8-37) (10(-6) M), while that of 10(-7) M PAMP did not, thereby suggesting that this last peptide acts through specific receptors. Collectively, these findins may suggest that of the two main preproadrenomedullin derived peptides is PAMP which has probably to be considered a physiologic inhibitor of mineralocorticoid secretion in rats. [References: 17]
机译:肾上腺髓质素(ADM)和肾上腺髓质素N端20肽(PAMP)衍生自称为preproadrenomedullin的185个氨基酸的激素,在大鼠肾上腺髓质中高度表达。 ADM和PAMP既不影响分散的大鼠Zona肾小球细胞的基础刺激,也不影响ACTH刺激的醛固酮分泌。相比之下,两种肽均显着抑制了血管紧张素II刺激的醛固酮的产生,PAMP比ADM更为有效(最小有效浓度:10(-10)M与10(-8)M。IC50,2.0 +/- 0.17 x 10 (-9)M对3.1 +/- 0.22 x 10(-8)M; P <0.01。最大抑制率分别为80%和43%)。 1型降钙素基因相关肽(CGRP)受体CGRP(8-37)(10(-6)M)的竞争性拮抗剂完全逆转了10(-7)M ADM的抑制作用,而10( -7)M PAMP没有,因此表明该最后的肽通过特定的受体起作用。总的来说,这些发现蛋白可能暗示PAMP是两种主要的preproadrenomedullin衍生肽中的一种,它可能被认为是大鼠盐皮质激素分泌的生理抑制剂。 [参考:17]

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