中枢α_2肾上腺素受体与镇痛

中枢α_２肾上腺素受体与镇痛陈明辉，黄显奋（医学神经生物学国家重点实验室，上海医科大学神经生物学教研室，上海２０００３２）中文图书资料分类法分类号Ｒ９７１．１早在１９０４年，Ｗｅｂｅｒ就发现肾上腺素（ａｄｒｅｎａｌｉｎ，Ａ）有中枢镇痛作用，进一步的研?..

Clonidine Inhibits Phenylephrine-Induced Contraction of Rat Thoracic Aortae by Competitive Antagonism of α₁-Adrenoceptors Independent of α₂-Adrenoceptor Stimulation

Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.

右旋美托咪啶的抗炎作用研究进展

α2-肾上腺素受体激动剂-右旋美托咪啶选择性地与α2,α1肾上腺素能受体结合的比例为1 600∶1,与α2-AR的亲和力为可乐定的8倍。其半衰期也较可乐定短,分布半衰期大约为6分钟,消除半衰期大约为2小时,药代动力学方面的可预测性更强。

Anti-inflammatory and antipyretic potential of Arbutus andrachne L.methanolic leaf extract in rats

Objective:To explore the anti-inflammatory and antipyretic effects of methanolic leaf extract from Arbutus andrachne and its mechanism of action.Methods:Paw edema was induced by intraplantar(i.pl.)injection ofλ-carrageenan(1%w/v,100μL/paw)while pyrexia was evoked by intraperitoneal(i.p.)injection of 20% baker’s yeast(20 mL/kg body wt)in male Wistar rats.The anti-inflammatory and antipyretic effects of Arbutus andrachne methanolic leaf extract were explored by injecting rats with different doses of the plant extract(150,300,and 600 mg/kg body wt,i.p.).Selective antagonists for transient receptor potential vanilloid-1(TRPV1),cannabinoid receptor 1(CB1),and alpha-2 adrenergic receptor(α2-AR)were used to unravel the extracts’mechanism of action.Blood samples were collected from the heart of rats to measure the levels of interleukin-6(IL-6)and prostaglandin E2(PGE2)by enzyme-linked immunosorbent assay.Results:The extract exhibited potent anti-inflammatory activity by decreasing paw thickness and IL-6 levels.In addition,yeast-evoked pyrexia was attenuated by the extract treatment via TRPV1 and CB1 receptors and a reduction in PGE2 levels.No significant effects were found for α2-AR.Moreover,the rats that received the plant extract demonstrated similar responses to the positive control group.Conclusions:Arbutus andrachne can be a good candidate for treating inflammation and pyrexia and should be further investigated.

α2肾上腺素能受体激动剂对儿童体外循环时核因子-κB的影响

有研究表明体外循环所致的炎性反应引发了脑损伤，核因子-κB（NF-κB）在机体炎性反应中起着关键的作用，而Q2肾上腺素能受体（α2-AR）激动剂能够抑制机体的炎性反应。本研究旨在观察α2-AR激动剂对儿童体外循环时核因子-κB的影响。

α_(2A)-肾上腺素受体亚型

α2 -肾上腺素受体 (α2 - AR)亚型 α2 A- AR广泛分布在中枢神经系统和外周组织 ,通过偶联 Gi蛋白 ,介导诸如心脏功能的调节 ,中枢神经系统的调控等一系列重要的生理、生化和药理学效应。α2 A- AR的激动剂已广泛应用于高血压等疾病的防治。本文就 α2 A- AR的结构、信号转导、生物功能、调节。