Grześk G, Szadujkis-Szadurski L
Department of Pharmacology and Therapeutics, L. Rydygier Medical University of Bydgoszcz, Poland.
Pol J Pharmacol. 2001 Nov-Dec;53(6):605-13.
The inhibitory effect of lipopolysaccharides (LPS) on contraction evoked by alpha-adrenergic stimulation is quite well-known, but molecular mechanism of this inhibition is unclear. In the present study, an interaction between alpha-adrenoceptor response and LPS in rat tail artery was investigated using chemical stimulation. In the presence of LPS noradrenaline and phenylephrine, concentration-response curves were shifted to the right with a change in maximal responses. The K(A) and K(B) values calculated in the presence and absence of LPS did not differ significantly. The results strongly suggest that LPS did not change the affinity of alpha-adrenoceptors. Changes in the plot showing relationship between agonist-evoked responses and receptor occupancy in the presence of LPS and reduction of K(A)/ED50 value suggest reduction of alpha-adrenoceptor reserve. In the experiments performed on arteries without endothelium, the inhibitory effect of LPS was still present. In the presence of atropine, antazoline and indomethacin, the reduction of alpha-adrenoceptor reserve was noted, but in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME), the inhibitory effect of LPS was not significant. Moreover, in LPS-pretreated arteries, in the presence of L-NAME, the increase in the receptor reserve was observed. It suggests that inhibitory effect of LPS is partially reversible. The results strongly indicate that in early endotoxemia, main inhibitory effect of LPS is connected with releasing nitric oxide and decreasing coupling between alpha1-adrenoceptor and signal induction.
脂多糖（LPS）对α-肾上腺素能刺激诱发的收缩的抑制作用是广为人知的，但这种抑制作用的分子机制尚不清楚。在本研究中，利用化学刺激研究了大鼠尾动脉中α-肾上腺素能受体反应与LPS之间的相互作用。在LPS、去甲肾上腺素和苯肾上腺素存在的情况下，浓度-反应曲线向右移动，最大反应发生变化。在有和没有LPS的情况下计算出的K(A)和K(B)值没有显著差异。结果强烈表明，LPS没有改变α-肾上腺素能受体的亲和力。在LPS存在的情况下，显示激动剂诱发反应与受体占有率之间关系的图的变化以及K(A)/ED50值的降低表明α-肾上腺素能受体储备减少。在对无内皮的动脉进行的实验中，LPS的抑制作用仍然存在。在阿托品、安他唑啉和吲哚美辛存在的情况下，观察到α-肾上腺素能受体储备减少，但在N-ω-硝基-L-精氨酸甲酯（L-NAME）存在的情况下，LPS的抑制作用不显著。此外，在LPS预处理的动脉中，在L-NAME存在的情况下，观察到受体储备增加。这表明LPS的抑制作用部分是可逆的。结果强烈表明，在早期内毒素血症中，LPS的主要抑制作用与一氧化氮释放以及α1-肾上腺素能受体与信号诱导之间的偶联减少有关。
