Steinmetz M, Schlatter E, Boudier H A, Rahn K H, De Mey J G
Medizinische Poliklinik, Westfälische Wilhelms-Universität Münster, Germany.
J Pharmacol Exp Ther. 2000 Sep;294(3):1175-81.
The effects of diadenosine polyphosphates (APnA; n = 3-6) and adenine nucleotides on contractile reactivity of isolated rat mesenteric resistance arteries (MrA) and superior epigastric arteries (SEA), which display a dense and sparse autonomic innervation, respectively, were evaluated. All agonists examined, except adenosine and AMP, induced contractions. The rank order of potency was similar in both arteries: alpha,beta-methylene ATP (alpha,beta-meATP) > AP5A > AP6A > AP4A > ATP > ADP > AP3A. Contractions were stable during several minutes in SEA but highly transient in MrA. They were reduced after exposure to 10 microM alpha,beta-meATP and by 10 microM of the P2X antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. During phenylephrine (10 microM)-induced contractions, the agonists induced a further contraction in SEA. In MrA, however, further contraction was followed by marked relaxation. The rank order of relaxing potency was comparable to that of the contractile potency of agonists. Also, the relaxing effects of APnA were blunted by 10 microM pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and after exposure to alpha,beta-meATP. In vitro and in vivo sympathectomy with 6-hydroxydopamine and removal of the endothelium did not modify the effects of APnA in MrA. Thus, the contractile effects of APnA in resistance arteries 1) are due to a P2X purinoceptor-mediated stimulation of the smooth muscle; 2) depend on the length of the phosphate chain; and 3) are followed by endothelium-independent relaxing effects in MrA but not SEA, which may involve receptors that are similar to those mediating contraction. The regional heterogeneity of APnA effects cannot be attributed to a direct neurogenic influence.
评估了二腺苷多磷酸（APnA；n = 3 - 6）和腺嘌呤核苷酸对分离的大鼠肠系膜阻力动脉（MrA）和腹壁上动脉（SEA）收缩反应性的影响，这两种动脉分别表现出密集和稀疏的自主神经支配。除腺苷和AMP外，所有检测的激动剂均诱导收缩。两种动脉中激动剂的效价顺序相似：α,β-亚甲基ATP（α,β-meATP）> AP5A > AP6A > AP4A > ATP > ADP > AP3A。SEA中的收缩在几分钟内稳定，但在MrA中高度短暂。暴露于10 μM α,β-meATP和10 μM P2X拮抗剂磷酸吡哆醛 - 6 - 偶氮苯 - 2',4'-二磺酸后，收缩减弱。在去氧肾上腺素（10 μM）诱导的收缩过程中，激动剂在SEA中诱导进一步收缩。然而，在MrA中，进一步收缩后紧接着是明显的舒张。舒张效价顺序与激动剂的收缩效价顺序相当。此外，10 μM磷酸吡哆醛 - 6 - 偶氮苯 - 2',4'-二磺酸和暴露于α,β-meATP后，APnA的舒张作用减弱。用6 - 羟基多巴胺进行体外和体内交感神经切除术以及去除内皮均未改变APnA对MrA的作用。因此，APnA在阻力动脉中的收缩作用1）是由于P2X嘌呤受体介导的平滑肌刺激；2）取决于磷酸链的长度；3）在MrA中随后是不依赖内皮的舒张作用，而在SEA中则不然，这可能涉及与介导收缩的受体相似的受体。APnA作用的区域异质性不能归因于直接的神经源性影响。
