Atkinson B N, Minneman K P
Department of Pharmacology, Emory University Medical School, Atlanta, Georgia 30322.
J Neurochem. 1991 Feb;56(2):587-95. doi: 10.1111/j.1471-4159.1991.tb08190.x.
The adrenergic receptor subtypes involved in cyclic AMP responses to norepinephrine (NE) were compared between slices of rat cerebral cortex and primary neuronal and glial cultures from rat brain. In neuronal cultures, NE and the beta-adrenergic receptor agonist isoproterenol (ISO) caused similar increases in cyclic AMP, which were not altered by the alpha-adrenergic receptor antagonist phentolamine. In glial cultures, NE caused a much smaller cyclic AMP response than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists (phentolamine greater than yohimbine greater than prazosin). alpha 2-Adrenergic receptor agonists partially inhibited the ISO response in glial cultures to a level similar to that observed with NE alone (clonidine = UK 14,304 greater than NE greater than 6-fluoro-NE greater than epinephrine). In slices from cerebral cortex, NE caused a much larger increase in cyclic AMP than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists with a different order of potency (prazosin greater than phentolamine greater than yohimbine). alpha 1-Adrenergic receptor agonists potentiated the response to ISO to a level similar to that observed with NE alone (epinephrine = NE greater than phenylephrine greater than 6-fluoro-NE greater than methoxamine). In all three tissue preparations, large responses to both alpha 1-receptor activation (increases in inositol phosphate accumulation) and alpha 2-receptor activation (decreases in forskolin-stimulated cyclic AMP accumulation) were observed. These data indicate that all of the major adrenergic receptor subtypes (beta, alpha 1, alpha 2) are present in each tissue preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
比较了大鼠大脑皮层切片与大鼠脑原代神经元及神经胶质细胞培养物中参与去甲肾上腺素（NE）诱导的环磷酸腺苷（cAMP）反应的肾上腺素能受体亚型。在神经元培养物中，NE和β-肾上腺素能受体激动剂异丙肾上腺素（ISO）引起类似的cAMP增加，α-肾上腺素能受体拮抗剂酚妥拉明对此无影响。在神经胶质细胞培养物中，NE引起的cAMP反应比ISO小得多，α-肾上腺素能受体拮抗剂可逆转这种差异（酚妥拉明＞育亨宾＞哌唑嗪）。α2-肾上腺素能受体激动剂部分抑制神经胶质细胞培养物中的ISO反应，使其达到与单独使用NE时相似的水平（可乐定=UK 14,304＞NE＞6-氟-NE＞肾上腺素）。在大脑皮层切片中，NE引起的cAMP增加比ISO大得多，α-肾上腺素能受体拮抗剂以不同的效价顺序逆转了这种差异（哌唑嗪＞酚妥拉明＞育亨宾）。α1-肾上腺素能受体激动剂增强对ISO的反应，使其达到与单独使用NE时相似的水平（肾上腺素=NE＞去氧肾上腺素＞6-氟-NE＞甲氧明）。在所有三种组织制剂中，均观察到对α1受体激活（肌醇磷酸积累增加）和α2受体激活（福斯高林刺激的cAMP积累减少）的强烈反应。这些数据表明，所有主要的肾上腺素能受体亚型（β、α1、α2）都存在于每种组织制剂中。（摘要截短于250字）
