Bültmann R, Tuluc F, Starke K
Pharmakologisches Institut, Freiburg i. Br., Germany.
Eur J Pharmacol. 1998 Jun 19;351(2):209-15. doi: 10.1016/s0014-2999(98)00309-4.
Agonist and antagonist effects of the putative P2Y1 receptor antagonist adenosine 3'-phosphate 5'-phosphosulphate (PAPS) were studied in intact tissues. In the carbachol-precontracted guinea-pig taenia coli, PAPS caused prominent relaxation (EC50 3.3 microM). The response was attenuated by the P2 receptor antagonists 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS) and reactive red 2 with apparent Kd values (0.27 and 0.29 microM) indicating that PAPS acts through the non-P2Y receptor, which is the site of action of alpha,beta-methylene ATP (alpha,beta-MeATP) in the taenia coli. Incubation with PAPS (10-100 microM) attenuated the P2Y receptor-mediated relaxation caused by 5'-O-(2-thiodiphosphate) (ADPbetaS); PAPS (100 microM) also attenuated the relaxation caused by alpha,beta-MeATP, as well as the alpha1-adrenoceptor-mediated response to noradrenaline. In the noradrenaline-precontracted rat aorta, PAPS caused minor relaxation (EC50 24.7 microM), which was reduced by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS; 1 microM), indicating that PAPS activates endothelial P2Y receptors. Incubation with PAPS (10 and 100 microM) attenuated the P2Y receptor-mediated relaxation caused by ADPbetaS; PAPS (100 microM) also attenuated the P2U receptor-mediated relaxation caused by UTP and the muscarine receptor-mediated response to acetylcholine. In rat vas deferens, PAPS (100 microM) attenuated the P2X receptor-mediated contraction elicited by alpha,beta-MeATP but did not alter the alpha1-adrenoceptor-mediated response to noradrenaline. The results indicate that PAPS attenuates P2Y receptor-mediated relaxation in intact tissues. However, due to its limited subtype selectivity and non-P2 receptor effects, the nucleotide is not a suitable antagonist for this subtype.
在完整组织中研究了假定的P2Y1受体拮抗剂3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）的激动剂和拮抗剂作用。在卡巴胆碱预收缩的豚鼠结肠带中，PAPS引起显著舒张（EC50为3.3微摩尔）。该反应被P2受体拮抗剂4,4'-二异硫氰酸根合芪-2,2'-二磺酸（DIDS）和活性红2减弱，表观解离常数（Kd）值（分别为0.27和0.29微摩尔）表明PAPS通过非P2Y受体起作用，该受体是α,β-亚甲基ATP（α,β-MeATP）在结肠带中的作用位点。用PAPS（10 - 100微摩尔）孵育可减弱由5'-O-(2-硫代二磷酸酯)（ADPβS）引起的P2Y受体介导的舒张；PAPS（100微摩尔）也减弱了由α,β-MeATP引起的舒张以及α1-肾上腺素能受体介导的对去甲肾上腺素的反应。在去甲肾上腺素预收缩的大鼠主动脉中，PAPS引起轻微舒张（EC50为24.7微摩尔），该舒张被P2受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2',5'-二磺酸（异-PPADS；1微摩尔）减弱，表明PAPS激活内皮P2Y受体。用PAPS（10和100微摩尔）孵育可减弱由ADPβS引起的P2Y受体介导的舒张；PAPS（1百微摩尔）也减弱了由UTP引起的P2U受体介导的舒张以及毒蕈碱受体介导的对乙酰胆碱的反应。在大鼠输精管中PAPS（100微摩尔减弱α,β-MeATP引起的P - 介导的收缩，但不改变α1 - 肾上腺素能受体介导的对去甲肾上腺素反应。结果表明PAPS减弱完整组织中P2Y受体介导的舒张。然而，由于其有限的亚型选择性和非P2受体效应，该核苷酸不是该亚型合适拮抗剂。
