Female sex steroid hormones and pregnancy regulate receptors for calcitonin gene-related peptide in rat mesenteric arteries, but not in aorta.
Female sex steroid hormones and pregnancy regulate receptors for calcitonin gene-related peptide in rat mesenteric arteries, but not in aorta.
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雌性类固醇激素和妊娠调节大鼠肠系膜动脉中降钙素基因相关肽的受体，但不调节主动脉中的受体。
DOI：
10.1095/biolreprod.103.022467
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Gangula,PRR
中科院分区：
文献类型：
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作者：
Yallampalli,C;Kondapaka,SB;Lanlua,P;Wimalawansa,SJ;Gangula,PRR
降钙素基因相关肽(CGRP)是一种强大的血管扩张神经肽，参与调节血管张力。我们实验室和其他研究人员的研究结果表明，妊娠期间血管对降钙素基因相关肽的敏感性增强，女性类固醇激素雌二醇-17β(E2)和孕酮(P4)可能参与了这一过程。我们假设，在妊娠和性激素治疗期间，肠系膜动脉中的CGRP受体增加。在本研究中，我们研究了妊娠和雌性性类固醇激素对大鼠肠系膜动脉CGRP受体CGRP-A和CGRP-B的调节作用。CGRP-A受体由降钙素受体样受体(CRLR)和受体活性修饰蛋白1(RAMP1)组成，但CGRP-B受体的特性有待进一步研究。逆转录-聚合酶链式反应检测CRLR和RAMP1的信使RNA水平，Western印迹法检测CGRP-B受体蛋白水平。此外，通过Scatchard分析测定了[125I]CGRP的结合。随着妊娠的进行，肠系膜动脉中CGRP-A(CRLR和RAMP1)的mRNA和CGRP-B受体的蛋白表达均增加，与未怀孕的哺乳期动物相比。P4拮抗剂RU-486下调和上调妊娠大鼠肠系膜动脉的这些受体(P<；0.05)。在去卵巢的成年大鼠，P4上调CRLR和RAMP1mRNA水平以及[125I]CGRP结合部位。P4组和E2、P4联合组CGRP-B受体蛋白水平显著升高(P<0.05)。结合早期的研究结果，这些数据表明，肠系膜动脉CGRP-A(CRLR和RAMP1)和CGRP-B受体的表达增加可能在降低血管阻力和妊娠期间发生的血管适应中起重要作用；此外，P4可能参与了这一过程。
Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide known to be involved in the regulation of vascular tone. Results of previous studies from our laboratory and others suggest that vascular sensitivity to CGRP is enhanced during pregnancy and that the female sex steroid hormones estradiol-17β (E2) and progesterone (P4) may be involved in this process. We hypothesized that CGRP receptors in the mesenteric artery are increased during pregnancy and with sex steroid hormone treatments. In the present study, we investigated whether pregnancy and female sex steroid hormones modulate the CGRP-receptors CGRP-A and CGRP-B in the mesenteric artery in the rat. The CGRP-A receptor consists of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1); however, the CGRP-B receptor needs to be further characterized. Messenger RNA levels for CRLR and RAMP1were assessed by reverse transcription-polymerase chain reaction, and CGRP-B receptor proteins levels were determined by Western blot analysis. In addition, [125I]CGRP binding was measured by Scatchard analysis. Both mRNA for CGRP-A (CRLR and RAMP1) and the protein for CGRP-B receptors in mesenteric arteries were increased with pregnancy compared to nonpregnant, diestrous animals. A P4antagonist, RU-486, downregulated and P4upregulated these receptors in mesenteric arteries (P< 0.05) in pregnant rats. In adult ovariectomized rats, P4upregulated CRLR and RAMP1mRNA levels as well as [125I]CGRP-binding sites. The CGRP-B-receptor protein levels were significantly (P< 0.05) elevated by P4and by combined E2and P4treatment. Together with earlier findings, these data suggest that increases in the expression of CGRP-A (CRLR and RAMP1) and CGRP-B receptors in mesenteric arteries may be important in reducing vascular resistance and in vascular adaptations that occur during pregnancy; in addition, P4may be involved in this process.