Menkes H, Baraban J M, Snyder S H
Eur J Pharmacol. 1986 Mar 11;122(1):19-27. doi: 10.1016/0014-2999(86)90153-6.
To explore the function of protein kinase C in smooth muscle, the effects of phorbol esters, potent activators of protein kinase C, were examined in guinea-pig tracheal rings and ileal strips. In tracheal rings, phorbol-12,13-diacetate (PDA) and 12-deoxyphorbol-13-isobutyrate (DPB), both potent stimulants of protein kinase C, produce a concentration dependent, reversible relaxation of resting tracheal tension, whereas phorbol, an inactive analogue is ineffective. PDA also reverses contractions produced by carbachol, serotonin, prostaglandin F2 alpha and prostaglandin D2. In contrast to their ability to inhibit agonist induced contractions, PDA and DPB greatly amplify the constriction produced by a depolarizing concentration of KCl (59 mM). The calcium channel blockers verapamil, nifedipine and diltiazem block the constriction produced by KCl and PDA suggesting that under depolarizing conditions, PDA synergizes with increased intracellular calcium to potentiate muscle contraction. Similar biphasic responses to phorbol esters are elicited in strips of guinea-pig ileum. These results indicate that in addition to enhancing the actions of intracellular calcium in producing contraction, protein kinase C can also activate feedback mechanisms which limit cellular responses.
为了探究蛋白激酶C在平滑肌中的功能，研究了蛋白激酶C的强效激活剂佛波酯对豚鼠气管环和回肠肌条的影响。在气管环中，蛋白激酶C的两种强效刺激剂佛波醇-12,13-二乙酸酯（PDA）和12-脱氧佛波醇-13-异丁酸酯（DPB），可使静息气管张力产生浓度依赖性、可逆性松弛，而无活性类似物佛波醇则无效。PDA还可逆转由卡巴胆碱、5-羟色胺、前列腺素F2α和前列腺素D2引起的收缩。与它们抑制激动剂诱导收缩的能力相反，PDA和DPB极大地增强了由去极化浓度的氯化钾（59 mM）引起的收缩。钙通道阻滞剂维拉帕米、硝苯地平和地尔硫卓可阻断氯化钾和PDA引起的收缩，这表明在去极化条件下，PDA与细胞内钙增加协同作用以增强肌肉收缩。在豚鼠回肠肌条中也观察到对佛波酯类似的双相反应。这些结果表明，除了增强细胞内钙在产生收缩中的作用外，蛋白激酶C还可激活限制细胞反应的反馈机制。
