Kageyama Kazunori, Furukawa Ken-Ichi, Miki Izumi, Terui Ken, Motomura Shigeru, Suda Toshihiro
Third Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.
J Cardiovasc Pharmacol. 2003 Oct;42(4):561-5. doi: 10.1097/00005344-200310000-00015.
Four corticotropin-releasing factor (CRF)-related peptides have been found in mammals and are known as CRF, urocortin, urocortin II, and urocortin III (also known as stresscopin). The three urocortins have considerably higher affinities for CRF receptor type 2 (CRF R2) than CRF, and urocortin II and urocortin III are highly selective for CRF R2. In the present study, the authors examined the hypothesis that urocortin II or urocortin III, in addition to urocortin, produces vasodilation as a candidate for natural ligands of CRF R2beta in rat thoracic aorta. Involvement of protein kinases on urocortin-induced vasodilation was also explored. The vasodilative effects of urocortin II and urocortin III were more potent than that of CRF, but less potent than that of urocortin. Urocortin II-induced vasodilation was significantly attenuated by a CRF R2-selective antagonist, antisauvagine-30. Both SQ22536, an adenylate cyclase inhibitor, and Rp-8-Br-cAMPS, a protein kinase A (PKA) inhibitor, were found to attenuate the urocortin II-induced vasodilation. SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, also inhibited the effects of urocortin and urocortin II on vasodilation. Thus, urocortins contribute to vasodilation via p38 MAP kinase as well as PKA pathways.
在哺乳动物中已发现四种促肾上腺皮质激素释放因子（CRF）相关肽，即CRF、尿皮质素、尿皮质素II和尿皮质素III（也称为应激肽）。三种尿皮质素对2型CRF受体（CRF R2）的亲和力比CRF高得多，且尿皮质素II和尿皮质素III对CRF R2具有高度选择性。在本研究中，作者检验了以下假设：除尿皮质素外，尿皮质素II或尿皮质素III可产生血管舒张作用，作为大鼠胸主动脉中CRF R2β天然配体的候选物。还探讨了蛋白激酶在尿皮质素诱导的血管舒张中的作用。尿皮质素II和尿皮质素III的血管舒张作用比CRF强，但比尿皮质素弱。尿皮质素II诱导的血管舒张被CRF R2选择性拮抗剂反蛙皮素-30显著减弱。腺苷酸环化酶抑制剂SQ22536和蛋白激酶A（PKA）抑制剂Rp-8-Br-cAMPS均被发现可减弱尿皮质素II诱导的血管舒张。p38丝裂原活化蛋白（MAP）激酶抑制剂SB203580也抑制了尿皮质素和尿皮质素II对血管舒张的作用。因此，尿皮质素通过p38 MAP激酶以及PKA途径促进血管舒张。
