Sullivan T J, Parker K L, Eisen S A, Parker C W
J Immunol. 1975 May;114(5):1480-5.
Changes in intracellular and extracellular rat mast cell adenosine 3':5' monophosphate (cAMP) concentrations during stimulation of histamine release by 48/80 were studied. There was a rapid and progressive fall in intracellular cAMP beginning within 10 sec after the addition of 48/80. The lowest cAMP values were obtained at 10 min, with return to control levels by 30 min. The fall in cAMP was dose-related with progressive decreases in 10-min cAMP measurements as the 48/80 concentration was increased from 0.25 to 1.00 mug/ml. There was a graded increase in histamine release over the same concentration range. Attempts to demonstrate significant amounts of cAMP in the medium during 48/80 stimulation were unsuccessful, indicating that the changes in cAMP intracellularly are not due to altered cellular permeability. There was a general correlation between the ability of pharmacologic agents to sustain high intracellular levels of cAMP in the presence of 48/80, and inhibition of histamine release. Theophylline (20 mM) which increased cAMP levels 2- 3-fold prevented a detectable decrease in cAMP after 1 mug/ml 48/80 (measured at 10 min) and almost completely inhibited histamine release. Prostaglandin E1 (27 muM) also raised cAMP levels, decreased the 48/80-induced fall in cAMP (by 42%). Epinephrine increased mast cell cAMP levels, but did not prevent the subsequent 48/80-induced decrease in cAMP and did not inhibit histamine release. Carbamylcholine (1 nM), adenine (1 muM), and diazoxide (10 muM) lowered mast cell cAMP and potentiated 48/80 induced release. In view of previous studies from this laboratory indicating that 48/80 stimulates mast cell phosphodiesterase, it seems likely that the 48/80-induced fall in cAMP is due, at least in part, to increased cAMP destruction. Since agents which prevent the fall in cAMP inhibit histamine release, it is apparent that cAMP is an important part of the control mechanism of histamine secretion. On the other hand, it cannot be concluded that a decrease in cAMP alone is sufficient to produce a response since carbamylcholine, diazoxide, and adenine which lower cAMP do not alter histamine release unless 48/80 is also present.
研究了48/80刺激大鼠肥大细胞组胺释放过程中细胞内和细胞外3':5'-环磷酸腺苷（cAMP）浓度的变化。加入48/80后10秒内，细胞内cAMP迅速且持续下降。10分钟时cAMP降至最低值，30分钟时恢复至对照水平。cAMP的下降与剂量相关，随着48/80浓度从0.25微克/毫升增加到1.00微克/毫升，10分钟时cAMP测量值逐渐降低。在相同浓度范围内，组胺释放呈分级增加。在48/80刺激期间，试图证明培养基中存在大量cAMP未成功，这表明细胞内cAMP的变化并非由于细胞通透性改变。在48/80存在的情况下，药理试剂维持细胞内高cAMP水平的能力与组胺释放的抑制之间存在普遍相关性。茶碱（20毫摩尔）使cAMP水平升高2至3倍，可防止1微克/毫升48/80作用后（10分钟时测量）cAMP出现可检测到的下降，并几乎完全抑制组胺释放。前列腺素E1（27微摩尔）也提高了cAMP水平，减少了48/80诱导的cAMP下降（降低42%）。肾上腺素增加肥大细胞cAMP水平，但不能防止随后48/80诱导的cAMP下降，也不能抑制组胺释放。氨甲酰胆碱（1纳摩尔）、腺嘌呤（1微摩尔）和二氮嗪（10微摩尔）降低肥大细胞cAMP并增强48/80诱导的释放。鉴于本实验室先前的研究表明48/80刺激肥大细胞磷酸二酯酶，48/80诱导的cAMP下降似乎至少部分是由于cAMP破坏增加所致。由于防止cAMP下降的试剂抑制组胺释放，显然cAMP是组胺分泌控制机制的重要组成部分。另一方面，不能得出仅cAMP下降就足以产生反应的结论，因为降低cAMP的氨甲酰胆碱、二氮嗪和腺嘌呤除非同时存在48/80，否则不会改变组胺释放。
