Fone K C, Johnson J V, Putland A P, Bennett G W
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, England.
J Neurochem. 1991 Sep;57(3):845-51. doi: 10.1111/j.1471-4159.1991.tb08228.x.
The release of endogenous noradrenaline (NA) from slices of adult rat brainstem and ventral thoracic spinal cord was investigated using a fixed-volume incubation technique and HPLC with electrochemical detection. Incubation with potassium (15-50 mM) produced a dose-related increase in basal NA release that was calcium dependent. The potassium-evoked release of NA from spinal cord or brainstem slices was potentiated according to dose by preincubation with either (a) the selective alpha 2-adrenoceptor antagonist idazoxan (10(-6)-10(-4) M) or (b) the thyrotrophin-releasing hormone (TRH) analogue RX 77368 (pGlu-His-3,3'-dimethyl ProNH2; 10(-5) and 10(-4) M). Incubation of spinal cord slices with the NA uptake inhibitor maprotiline (1 microM) enhanced the effect of idazoxan but inhibited that of RX 77368. The effects of RX 77368 and potassium alone (15 mM) on NA release from both spinal cord and brainstem slices were reduced to basal levels with tetrodotoxin (10(-7) M). Similarly, preincubation of spinal cord, but not brainstem, slices with the insect neuropeptide proctolin (10(-4) M) significantly attenuated the potassium- or RX 77368-induced release of NA, whereas substance P (3 X 10(-5) and 1 X 10(-4) M) had no effect on either tissue. These results suggest that changes in NA release in the spinal cord and brainstem may mediate some of the actions of neuropeptides in ventral spinal cord, although the peptides may not be acting directly on the noradrenergic nerve terminals in these tissues.
采用固定体积孵育技术和带电化学检测的高效液相色谱法,研究了成年大鼠脑干和胸段脊髓腹侧切片中内源性去甲肾上腺素(NA)的释放情况。用钾(15 - 50 mM)孵育可使基础NA释放呈剂量相关增加,且该增加依赖于钙。脊髓或脑干切片中钾诱发的NA释放,通过以下预孵育可按剂量增强:(a)选择性α2 - 肾上腺素能受体拮抗剂咪唑克生(10^(-6) - 10^(-4) M)或(b)促甲状腺激素释放激素(TRH)类似物RX 77368(焦谷氨酸 - 组氨酸 - 3,3'-二甲基脯氨酰胺;10^(-5)和10^(-4) M)。用NA摄取抑制剂马普替林(1 μM)孵育脊髓切片可增强咪唑克生的作用,但抑制RX 77368的作用。单独使用RX 77368和钾(15 mM)对脊髓和脑干切片中NA释放的影响,在加入河豚毒素(10^(-7) M)后降至基础水平。同样,用昆虫神经肽普罗托林(10^(-4) M)预孵育脊髓切片(而非脑干切片)可显著减弱钾或RX 77368诱导的NA释放,而P物质(3×10^(-5)和1×10^(-4) M)对这两种组织均无影响。这些结果表明,脊髓和脑干中NA释放的变化可能介导了神经肽在脊髓腹侧的一些作用,尽管这些肽可能并非直接作用于这些组织中的去甲肾上腺素能神经末梢。