Suleyman H, Halici Z, Cadirci E, Hacimuftuoglu A, Bilen H
Department of Pharmacology, Erzurum, Ataturk University, Faculty of Medicine, Turkey.
J Physiol Pharmacol. 2008 Dec;59(4):661-72.
In this study we investigated both intact and adrenalectomized rats to determine whether or not the anti-inflammatory effects of indomethacin, diclofenac sodium, ibuprofen, nimesulide, tenoxicam and aspirin (IDINTA) are related to adrenal gland hormones in carrageenan-induced inflammation model of rats. Also, we investigated the anti-inflammatory action mechanism of hormones (adrenalin, cortisol) which perform a role in the anti-inflammatory effect of IDINTAon the adrenergic receptors. he results show that IDINTA produces significant anti-inflammatory effects in intact rats (ID(50): 9.82, 10.81, 95.21, 75.23, 8.21 and 61.84 mg/kg), but insignificant effects in adrenalectomized rats (ID(50): 152.97, 188.17, 1275.0, 433.67, 188.16 and 1028.17 mg/kg). In addition, adrenalin and prednisolone caused anti-inflammatory effect rates of 78.3% and 95.7% respectively in adrenalectomized rats. The anti-inflammatory effects of adrenalin and prednisolone did not change when prazosin (alpha(1)-receptor blocker), yohimbine (alpha(2)a2-receptor blocker) and phenoxybenzamine (alpha(2)- and alpha(2)-receptor blocker) were given to rat groups; however, in adrenalectomized rats administered with propranolol (a non-selective blocker of beta(1) and beta(2)-receptors) the anti-inflammatory effect of adrenalin was lost, and that of prednisolone decreased to 36.2%. It was also found that metoprolol (a selective blocker of beta(1)-receptors) did not alter the anti-inflammatory effects of the drugs. As a result, it was shown that anti-inflammatory effects of IDINTA are related to adrenalin and cortisol (corticosterone in rats). It was also determined for the first time that adrenalin (totally) and prednisolone (partially) triggered anti-inflammatory effects via the beta(2)-receptors but not via the alpha(1), alpha(2) and beta(1)-receptors.
在本研究中，我们对完整大鼠和肾上腺切除大鼠进行了研究，以确定吲哚美辛、双氯芬酸钠、布洛芬、尼美舒利、替诺昔康和阿司匹林（IDINTA）的抗炎作用是否与角叉菜胶诱导的大鼠炎症模型中的肾上腺激素有关。此外，我们还研究了在IDINTA抗炎作用中发挥作用的激素（肾上腺素、皮质醇）对肾上腺素能受体的抗炎作用机制。结果表明，IDINTA在完整大鼠中产生显著的抗炎作用（ID50：9.82、10.81、95.21、75.23、8.21和61.84mg/kg），但在肾上腺切除大鼠中作用不显著（ID50：152.97、188.17、1275.0、433.67、188.16和1028.17mg/kg）。此外，肾上腺素和泼尼松龙在肾上腺切除大鼠中的抗炎有效率分别为78.3%和95.7%。当给大鼠组给予哌唑嗪（α1受体阻滞剂）、育亨宾（α2a2受体阻滞剂）和酚苄明（α2和α2受体阻滞剂）时，肾上腺素和泼尼松龙的抗炎作用没有改变；然而，在给予普萘洛尔（β1和β2受体的非选择性阻滞剂）的肾上腺切除大鼠中，肾上腺素的抗炎作用消失，泼尼松龙的抗炎作用降至36.2%。还发现美托洛尔（β1受体的选择性阻滞剂）不会改变药物的抗炎作用。结果表明，IDINTA的抗炎作用与肾上腺素和皮质醇（大鼠中的皮质酮）有关。还首次确定，肾上腺素（完全）和泼尼松龙（部分）通过β2受体而非α1、α2和β1受体触发抗炎作用。
