Bradley M E, Kuenzli K A, Buxton I L
Department of Pharmacology, University of Nevada School of Medicine, Reno.
J Pharmacol Exp Ther. 1993 Mar;264(3):1033-9.
Cyclooxygenase products are thought to mediate adenosine-stimulated contraction of nonpregnant myometrium. We have examined the effects of the cyclooxygenase inhibitors, indomethacin and meclofenamate, upon adenosine-stimulated contractions in isolated, endometrium-free strips of uterine smooth muscle from virgin guinea pigs. Indomethacin (30 microM) had no effect on adenosine-induced contractions; addition of meclofenamate at 30 microM, however, rapidly and reversibly blocked contractions in response to adenosine, yet had no effect upon acetylcholine-stimulated contractions. Application of prostaglandin F2 alpha at a final concentration of 1.1 microM elicited contractions in indomethacin-treated (but not meclofenamate-treated) tissues. The adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline, interfered with adenosine-mediated contractions when present at a final concentration of 100 microM, confirming the presence of extracellular binding sites for the purine on the smooth muscle. Treatment of muscle strips with either of the adenosine uptake blockers, dipyridamole or S-(p-nitrobenzyl)-6-thio-guanosine, resulted in dramatic reductions in adenosine-stimulated contractions, findings consistent with an additional, intracellular site of action of adenosine in uterine smooth muscle. These results suggest that, in contrast to findings in intact strips of whole uterine tissue, cyclooxygenase activity is not required for adenosine-stimulated contraction in isolated myometrium from nonpregnant guinea pig. It also is suggested that the nonsteroidal anti-inflammatory compound, meclofenamate, may interfere with the binding of another (non-cyclooxygenase) product of arachidonic acid metabolism.
环氧化酶产物被认为介导腺苷刺激的非妊娠子宫肌层收缩。我们研究了环氧化酶抑制剂吲哚美辛和甲氯芬那酸对来自处女豚鼠的离体、无子宫内膜的子宫平滑肌条中腺苷刺激收缩的影响。吲哚美辛（30微摩尔）对腺苷诱导的收缩没有影响；然而，加入30微摩尔的甲氯芬那酸可迅速且可逆地阻断对腺苷的收缩反应，但对乙酰胆碱刺激的收缩没有影响。以1.1微摩尔的终浓度应用前列腺素F2α可在吲哚美辛处理（而非甲氯芬那酸处理）的组织中引起收缩。腺苷受体拮抗剂8 - （对 - 磺基苯基）茶碱在终浓度为100微摩尔时会干扰腺苷介导的收缩，证实了平滑肌上存在嘌呤的细胞外结合位点。用腺苷摄取阻滞剂双嘧达莫或S - （对 - 硝基苄基） - 6 - 硫代鸟苷处理肌条会导致腺苷刺激收缩显著减少，这些结果与腺苷在子宫平滑肌中的另一个细胞内作用位点一致。这些结果表明，与完整子宫组织条的研究结果相反，在非妊娠豚鼠的离体子宫肌层中，腺苷刺激的收缩不需要环氧化酶活性。还表明非甾体抗炎化合物甲氯芬那酸可能会干扰花生四烯酸代谢的另一种（非环氧化酶）产物的结合。
