Opposing functions of α- and β-adrenoceptors in the formation of processes by cultured astrocytes
Opposing functions of α- and β-adrenoceptors in the formation of processes by cultured astrocytes
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DOI：
10.1016/j.jphs.2020.12.005
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发表时间：
2021-01-08
影响因子：
3.5
通讯作者：
Otsuguro, Ken-ichi
中科院分区：
文献类型：
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作者：
Kitano, Taisuke;Eguchi, Ryota;Otsuguro, Ken-ichi
星形胶质细胞是具有许多精细突起的神经胶质细胞，其对于中枢神经系统的功能是重要的。β-肾上腺素受体的激活通过环腺苷酸（cAMP）信号传导诱导星形胶质细胞的突起形成。然而，α-肾上腺素受体在星形胶质细胞形态中的作用尚未阐明。在这里，我们研究了它通过使用培养的星形胶质细胞从新生大鼠脊髓和皮质。这些细胞暴露于去甲肾上腺素和β-肾上腺素受体激动剂异丙肾上腺素增加细胞内cAMP水平，并诱导形成的过程。α（1）-肾上腺素受体拮抗剂哌唑嗪和α（2）-肾上腺素受体拮抗剂阿替美唑可增强去甲肾上腺素诱导的突起形成。阿替美唑也增强去甲肾上腺素诱导的cAMP升高。异丙肾上腺素诱导的突起形成不受α（1）-肾上腺素受体激动剂苯肾上腺素的抑制，但受α（2）-肾上腺素受体激动剂右美托咪定的抑制。右美托咪定还可抑制腺苷酸环化酶激活剂毛喉素和膜渗透性cAMP类似物二丁酰-cAMP诱导的突起形成。此外，右美托咪定抑制腺苷或Rho相关激酶抑制剂Y27632诱导的cAMP非依赖性过程形成。在普萘洛尔的存在下，去甲肾上腺素抑制Y27632诱导的过程形成，这是由哌唑嗪或阿替美唑废除。这些结果表明，α-肾上腺素受体抑制cAMP依赖性和非依赖性星形胶质细胞的过程形成。(C)2020年，任作家。Elsevier B. V.代表日本药理学会制作和主办。
Astrocytes are glial cells with numerous fine processes which are important for the functions of the central nervous system. The activation of beta-adrenoceptors induces process formation of astrocytes via cyclic AMP (cAMP) signaling. However, the role of alpha-adrenoceptors in the astrocyte morphology has not been elucidated. Here, we examined it by using cultured astrocytes from neonatal rat spinal cords and cortices. Exposure of these cells to noradrenaline and the beta-adrenoceptor agonist isoproterenol increased intracellular cAMP levels and induced the formation of processes. Noradrenaline-induced process formation was enhanced with the alpha(1)-adrenoceptor antagonist prazosin and alpha(2)-adrenoceptor antagonist atipamezole. Atipamezole also enhanced noradrenaline-induced cAMP elevation. Isoproterenol-induced process formation was not inhibited by the alpha(1)-adrenoceptor agonist phenylephrine but was inhibited by the alpha(2)-adrenoceptor agonist dexmedetomidine. Dexmedetomidine also inhibited process formation induced by the adenylate cyclase activator forskolin and the membrane-permeable cAMP analog dibutyryl-cAMP. Moreover, dexmedetomidine inhibited cAMP-independent process formation induced by adenosine or the Rho-associated kinase inhibitor Y27632. In the presence of propranolol, noradrenaline inhibited Y27632-induced process formation, which was abolished by prazosin or atipamezole. These results demonstrate that alpha-adrenoceptors inhibit both cAMP-dependent and -independent astrocytic process formation. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.