佛波酯通过激活钠钾ATP酶抑制平滑肌收缩。

Phorbol esters inhibit smooth muscle contractions through activation of Na(+)-K(+)-ATPase.

Sasaguri T, Watson S P

Department of Pharmacology, University of Oxford.

Br J Pharmacol. 1990 Feb;99(2):237-42. doi: 10.1111/j.1476-5381.1990.tb14687.x.

Abstract

The role of protein kinase C (PKC) in agonist-induced contractions of guinea-pig ileum longitudinal smooth muscle has been investigated. 2. The phorbol esters, phorbol 12,13-dibutyrate (PDBu), phorbol 12,13-diacetate (PDA) and phorbol 12-myristate 13-acetate (PMA), relaxed tissues precontracted by submaximal concentrations of carbachol, histamine or substance P. 3. This inhibitory action of the phorbol esters was reversed following the application of ouabain, a specific inhibitor of Na(+)-K(+)-ATPase. Similarly, pretreatment with ouabain inhibited the ability of phorbol esters to relax tissues precontracted by the above agonists. 4. The slow relaxation of the tonic component of contraction induced by submaximal concentrations of carbachol and histamine, and all concentrations of substance P, was abolished in the presence of ouabain. 5. In Na(+)-loaded tissues, PDBu and carbachol caused a concentration-dependent increase of Na(+)-K(+)-ATPase activity, assessed by ouabain-sensitive 86Rb(+)-uptake. Extrusion of Na+, assessed by the cellular content of the ion, was also stimulated by PDBu (the effect of carbachol was not investigated). 6. We conclude that phorbol esters inhibit the tonic component of contractions induced by submaximal concentrations of these agonists through activation of Na(+)-K(+)-ATPase. We suggest that PKC may exert feedback control over the tonic component of agonist contractions through stimulation of the pump.

摘要

研究了蛋白激酶C（PKC）在豚鼠回肠纵行平滑肌激动剂诱导收缩中的作用。2. 佛波酯，佛波醇12,13 - 二丁酸酯（PDBu）、佛波醇12,13 - 二乙酸酯（PDA）和佛波醇12 - 肉豆蔻酸13 - 乙酸酯（PMA），可使由亚最大浓度的卡巴胆碱、组胺或P物质预收缩的组织松弛。3. 应用哇巴因（一种Na⁺-K⁺-ATP酶的特异性抑制剂）后，佛波酯的这种抑制作用被逆转。同样，用哇巴因预处理可抑制佛波酯使上述激动剂预收缩组织松弛的能力。4. 在哇巴因存在的情况下，由亚最大浓度的卡巴胆碱和组胺以及所有浓度的P物质诱导的收缩的强直成分的缓慢松弛被消除。5. 在Na⁺负载的组织中，PDBu和卡巴胆碱通过哇巴因敏感的⁸⁶Rb⁺摄取评估，引起Na⁺-K⁺-ATP酶活性的浓度依赖性增加。通过离子的细胞含量评估的Na⁺外流也受到PDBu的刺激（未研究卡巴胆碱的作用）。6. 我们得出结论，佛波酯通过激活Na⁺-K⁺-ATP酶抑制这些激动剂亚最大浓度诱导的收缩的强直成分。我们认为PKC可能通过刺激泵对激动剂收缩的强直成分发挥反馈控制作用。