Noguchi M, Ikarashi Y, Yuzurihara M, Mizoguchi K, Kurauchi K, Chen J-T, Ishige A
Kampo and Pharmacognosy Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
J Endocrinol. 2002 Oct;175(1):177-83. doi: 10.1677/joe.0.1750177.
We investigated the mechanism for the augmentation of the calcitonin gene-related peptide (CGRP)-induced elevation of skin temperature in ovariectomized (OVX) rats. I.v. injection of alphaCGRP (10 micro g/kg) elevated skin temperature of the hind paws. The elevation was significantly greater in OVX rats than in sham-operated rats and was inhibited by pretreatment with human CGRP(8-37) (100-1000 micro g/kg i.v.), a CGRP receptor antagonist, in a dose-dependent manner. In addition, ovariectomy not only potentiated vasorelaxation due to alphaCGRP but increased the number of CGRP receptors in mesenteric arteries. Further, the plasma concentration of endogenous CGRP was significantly lower in OVX rats. These results suggest that the low concentration of plasma CGRP due to ovarian hormone deficiency may induce the increase in the number of CGRP receptors due to up-regulation. Therefore, the increased number of CGRP receptors may be responsible for potentiation of exogenous alphaCGRP-induced elevation of skin temperature in OVX rats. The mechanism underlying the hot flashes observed in menopausal women may also involve, in part, the up-regulation of CGRP receptors following ovarian hormone deficiency.
我们研究了去卵巢（OVX）大鼠中降钙素基因相关肽（CGRP）诱导的皮肤温度升高增强的机制。静脉注射αCGRP（10μg/kg）可使后爪皮肤温度升高。OVX大鼠的这种升高明显大于假手术大鼠，并且以剂量依赖的方式被CGRP受体拮抗剂人CGRP（8 - 37）（100 - 1000μg/kg静脉注射）预处理所抑制。此外，去卵巢不仅增强了αCGRP引起的血管舒张，还增加了肠系膜动脉中CGRP受体的数量。此外，OVX大鼠内源性CGRP的血浆浓度显著降低。这些结果表明，由于卵巢激素缺乏导致的血浆CGRP低浓度可能通过上调诱导CGRP受体数量增加。因此，CGRP受体数量增加可能是OVX大鼠中外源性αCGRP诱导的皮肤温度升高增强的原因。绝经后女性中观察到的潮热的潜在机制可能也部分涉及卵巢激素缺乏后CGRP受体的上调。
