Haass M, Cheng B, Richardt G, Lang R E, Schömig A
Department of Cardiology, University of Heidelberg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):71-8. doi: 10.1007/BF00165129.
The relationship between noradrenaline and neuropeptide Y (NPY) release was investigated in the in situ perfused guinea pig heart with intact sympathetic innervation. For determination of NPY concentrations in the perfusate, a specific radioimmunoassay was employed and further characterized. Electrical stimulation of the left stellate ganglion (4, 8, 12, and 50 Hz; for 10 min) evoked a calcium-dependent and frequency-related overflow of noradrenaline and NPY, which was positively correlated (r = 0.83; p less than 0.001; n = 25). When two subsequent stimulations (12 Hz; each for 1 min) were performed in the same heart, addition of noradrenaline (10 microM) 5 min prior to the second stimulation reduced NPY overflow by 43 +/- 10%. The stimulated release of noradrenaline and NPY was increased by the alpha 2-adrenoceptor antagonist yohimbine (1 microM) to 170 +/- 10% and 199 +/- 26%, and attenuated by the alpha 2-adrenoceptor agonist B-HT 920 (1 microM) to 70 +/- 9% and 68 +/- 9%, respectively. The adenosine analogue cyclohexyladenosine (1 microM) significantly reduced the stimulated overflow of both noradrenaline (to 57 +/- 5%) and NPY (to 73 +/- 8%). Exogenous NPY (100 nM) attenuated the stimulated overflow of noradrenaline by 30 +/- 6%. Uptake1 blockade with desipramine (100 nM) or nisoxetine (100 nM) prior to the second stimulation significantly increased noradrenaline overflow and attenuated that of NPY; the attenuation of the stimulation-evoked overflow of NPY was abolished by yohimbine (1 microM). Our results indicate that electrical stimulation induces a calcium-dependent, exocytotic co-release of noradrenaline and NPY.(ABSTRACT TRUNCATED AT 250 WORDS)
在具有完整交感神经支配的原位灌注豚鼠心脏中，研究了去甲肾上腺素与神经肽Y（NPY）释放之间的关系。为了测定灌注液中的NPY浓度，采用了一种特异性放射免疫测定法并进行了进一步表征。电刺激左星状神经节（4、8、12和50Hz；持续10分钟）引起去甲肾上腺素和NPY的钙依赖性且与频率相关的溢出，二者呈正相关（r = 0.83；p < 0.001；n = 25）。当在同一心脏中进行两次连续刺激（12Hz；每次持续1分钟）时，在第二次刺激前5分钟加入去甲肾上腺素（10μM）可使NPY溢出减少43±10%。α2 -肾上腺素能受体拮抗剂育亨宾（1μM）可使去甲肾上腺素和NPY的刺激释放分别增加至170±10%和199±26%，而α2 -肾上腺素能受体激动剂B - HT 920（1μM）则分别使其减弱至70±9%和68±9%。腺苷类似物环己基腺苷（1μM）显著降低了去甲肾上腺素（降至57±5%）和NPY（降至73±8%）的刺激溢出。外源性NPY（100nM）使去甲肾上腺素的刺激溢出减少30±6%。在第二次刺激前用去甲丙咪嗪（100nM）或尼索西汀（100nM）阻断摄取1可显著增加去甲肾上腺素溢出并减弱NPY溢出；育亨宾（1μM）可消除刺激引起的NPY溢出减弱。我们的结果表明，电刺激诱导了去甲肾上腺素和NPY的钙依赖性、胞吐性共同释放。（摘要截短至250字）
