痛啡肽抑制电场刺激引起的大鼠气道胆碱能收缩反应(英文)

目的:研究痛啡肽(nociceptin)对大鼠离体气管/支气管的胆碱能神经兴奋所致收缩的抑制作用.方法:记录电场刺激引起胆碱能神经兴奋所致的标本收缩张力,了解nociceptin的作用.结果:Nociceptin0.001-0.1μmol/L可抑制标本的胆碱能收缩,其IC_(50)(95％的可信限)分别是0.06(0.04-0.08)μmol/L和0.07(0.05-0.1)μmol/L.在气管和支气管上,nociceptin 0.01μmol/L的抑制率分别是:(58±32)％和(60±26)％;预用纳洛酮0.1μmol/L后,nociceptin的抑制率为:(60±19)％和(54±20)％(P>0.05).Nociceptin 0.01μmol/L不影响外源性乙酰胆碱引起的气道标本收缩.κ阿片受体激动剂U-50488H 0.01—1 μmol/L不影响电场刺激引起的大鼠气道胆碱能收缩.结论:痛啡肽抑制电刺激引起的大鼠气道胆碱能收缩反应,且不受纳洛酮影响.     

DDPH抑制豚鼠单个心室肌细胞L-钙电流和钠电流(英文)

目的:研究1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐(DDPH)对豚鼠心室肌细胞L-型钙电流和钠电流的作用。方法:全细胞膜片箝技术。结果:(1)DDPH(3-300μmol·L~(-1))浓度依赖性地抑制L-型钙电流,IC_(50)为28.5μmol·L~(-1)(95％可信限:14.3-42.7μmol·L~(-1))。维拉帕米0.3-30μmol/L浓度依赖性地抑制钙电流,IC_(50)为1.8μmol·L~(-1)(95％可信限:1.3-2.3μmol·L~(-1))。美西律100μmol·L~(-1)对钙电流无影响。DDPH30μmol·L~(-1)使用依赖性阻滞钙电流,1Hz时抑制率为58％±13％(n=5,P<0.01),3Hz时为76％±11％(n=5,P<0.01)。(2)DDPH(20-320μmol·L~(-1))浓度依赖性抑制钠电流,IC_(50)为89.0μmol·L~(-1)(95％可信限:68.7-109.3μmol·L~(-1))。美西律抑制钠电流的IC_(50)为32.2μmol·L~(-1)(95％可信限:11.7-52.7μmol·L~(-1))。维拉帕米10μmol·L~(-1)对钠电流无影响(P>0.05).DDPH80μmol·L~(-1)对钠电流无使用依赖性阻滞。结论:DDPH抑制豚鼠心室肌细胞L-型钙电流和钠电流,但抑制钙电流的作用弱于维拉帕米,抑制钠电流的作用弱于美西律。     

阿片类药物在豚鼠离体回肠中的交互依赖性和交互耐受性

研究了阿片类药物在豚鼠离体回肠中的交互依赖性和交互耐受性. 豚鼠回肠分别与羟甲芬太尼(OMF 1 nmol·L^-1), D-Ala², D-Leu⁵-脑啡肽(DADLE, 0.3 μmol·L^-1)或U50488H (50 nmol·L^-1)在37℃温育4 h,它们相互及自身均能抑制纳洛酮(0.1 μmol·L^-1)或Mr2266 (0.1 μmol·L^-1)引起的戒断性收缩. 它们也能自身预先阻断戒断性收缩的产生. U50488H能预先阻断OMF, DADLE温育后纳洛酮所产生的戒断性收缩, 但后两者不能预先阻断U50488H 温育后由Mr2266所产生的戒断性收缩, 并且OMF和DADLE之间也不能相互阻断. 豚鼠回肠分别与OMF(1 nmol·L^-1), DADLE(0.3 μmol·L^-1) 在37℃ 温育2 h后, 对去甲吗啡(NM), OMF, DADLE的敏感性明显下降, 浓度反应曲线右移, 但对U50488H不产生耐受. 在U50488H (10 nmol·L^-1) 中温育1 h的回肠, 对U50488H的敏感性下降, 浓度反应曲线右移, 但对OMF, NM, DADLE的敏感性不变. 这些结果表明豚鼠回肠中μ, κ阿片受体是分离的.     

呋喃二氢吡啶Ⅰ对豚鼠心肌收缩力及动作电位的影响

呋喃二氢吡啶I(FDP I)呈浓度依赖性地抑制豚鼠心肌收缩力,IC_(50)为1.62μmol·L~1,并能抑制心肌静息后增强效应.成对刺激及正阶梯现象的收缩幅度,离体心乳头状肌细胞跨膜电位实验表明:FDPI 1.0、4.0μmol·L~1能缩短动作电位之APD_(30)·APD_(50),APD_(90),硝苯碇(Nif)0.1.1.0,4.0μmol·L~1亦能缩短APD,但两药在所试浓度范围内,对APA和V_(max)均无明显影响。     

蓝萼甲素对兔血小板生成血小板活化因子及花生四烯酸代谢的影响

蓝萼甲素在浓度0.1～100μmol·L~(-1)时可抑制A23187刺激的免血小板生成血小板活化因子,其IC_(50)为0.47μmol·L~(-1),当其浓度为10,100μmol·L~(-1)时能抑制花生四烯酸诱导的兔血小板血栓素A_2生成同时升高前列腺素E_2,推测蓝萼甲素通过抑制血小板活化因子生物合成及选择性抑制血栓素A_2生成而抑制血小板激活。     

一氧化氮对豚鼠胃窦环行肌电活动和收缩运动的影响

目的:在体外研究一氧化氮对豚鼠胃窦环行肌电活动和收缩运动的影响。方法:用常规方法同时记录胃窦肌条的电活动和收缩运动。结果:在豚鼠胃窦环行肌条上,一氧化氮供体硝普钠(0.5μmol·L~(-1))能显著抑制电活动快波和运动。这种抑制作用不受河鲀毒、阿托品、酚妥拉明和普萘洛尔(各1 μmol·L~(-1))的影响(P>0.05),但可被亚甲基蓝(5μmol·L~(-1))和氧合血红蛋白(5μmol·L~(-1))明显减弱(P<0.01)。结论:一氧化氮抑制豚鼠胃窦环行肌电活动和收缩运动。这种抑制效应是通过一氧化氮对平滑肌细胞膜的直接作用和增加细胞内环磷酸鸟苷来实现的。     

粉防己碱对吗啡在离体豚鼠回肠中依赖性的作用(英文)

目的:研究粉防己碱(Tet)和尼莫地平(Nim)对吗啡在离体豚鼠回肠中戒断性反应的影响。方法:戒断性收缩由纳洛酮(1μmol·L~(-1))加入已在含吗啡(3μmol·L~(-1))的37.5℃ Krebs液中孵育4h的离体豚鼠回肠或加入从吗啡依赖豚鼠中取得的回肠引起。结果:离体豚鼠回肠在含吗啡的Krebs液中孵育4h,给Nim(0.01、0.05和0.1μmol·L~(-1))或Tet(1、10和50μmol·L~(-1))抑制其戒断性收缩。Nim和Tet体内或体外给药都能抑制吗啡依赖豚鼠离体回肠的戒断性收缩。结论:钙拮抗剂Nim和Tet抑制吗啡在离体豚鼠回肠的戒断性收缩。     

盐酸吲满氨酯及依色林对胆碱酯酶的抑制作用

用微量二硫-双-硝基苯甲酸(DTNB)法测定胆碱酯酶(ChE)活力,比较了盐酸吲满氨酯(TMDMC)与依色林抑制ChE的作用,对于电鳐AChE依色林表现为竞争性抑制,K_i=0.115 μmol·L~1,TMDMC表现为竞争与非竞争混合性抑制,K_i=3.870μmol·L~(-1),K_i=16.321μmol·L~(-1)依色林和TMDMC抑制小鼠脑匀浆ChE活力的IC_(50)分别为1.78和5.07μmol·L~1、抑制小鼠全血ChE活力的IC_(50)分别为19.52和3.60μmol·L~1,说明TMDMC与依色林虽属同类化合物,但它们的抑酶类型和对真,假性ChE的抑制强度是不同的。     

吴茱萸次碱和辣椒素对过敏反应所致血管收缩的影响

目的 研究吴茱萸次碱和辣椒素对过敏反应中抗原攻击所致血管收缩的影响。方法 豚鼠腹腔注射牛血清白蛋白预致敏,3周后分离胸主动脉,离体血管环用0.01 mg·mL-1牛血清白蛋白(抗原)攻击诱发血管过敏反应。血管张力变化通过张力换能器连接PowerLab生物信号采集系统连续记录。结果 抗原攻击能诱导豚鼠预致敏的离体胸主动脉收缩,苯海拉明能显著抑制抗原攻击所致的血管收缩;预先用较高浓度辣椒素(1 μmol·L-1)耗竭神经递质降钙素基因相关肽(CGRP)或用选择性CGRP受体拮抗剂CGRP8～37能增强抗原攻击所致缩血管效应;辣椒素(0.03 μmol·L-1或0.1μmol·L-1)促进内源性CGRP释放能显著降低抗原攻击所致血管的收缩效应。吴茱萸次碱(10μmol·L-1或30μmol·L-1)能显著降低抗原攻击所致血管的收缩效应,辣椒素受体阻滞药capsaz-epine和选择性CGRP受体阻滞药CGRP8～37均取消吴茱萸次碱对血管收缩的抑制效应。结论 血管过敏反应时,CGRP的释放增加,能拮抗组胺等物质的缩血管效应;吴茱萸次碱能显著抑制血管过敏反应时血管的收缩,其作用与激活辣椒素受体进而促进内源性CGRP释放有关。     

胺碘酮对离体心肌的负性肌力作用

对离体左,右心房肌,胺碘酮(Ami)1～100μmol·L~(-1)均有负性肌力作用,30μmol·L~1明显抑制心肌静息后收缩,正阶梯和成对刺激效应,1～10μmol·L~1使苯福林,异丙肾上腺素,组胺和CaCl_2正性肌力作用的量效曲线呈非竞争性拮抗作用,心肌动作电位和收缩力同步记录发现,Ami 30μmol·L~1减弱心肌收缩,延长APD,但对平台期和V_(max)无影响.故Ami的负性肌力作用可能是抑制心肌细胞外Ca~(2+)内流和细胞内Ca~(2+)释放所致,并非选择性阻滞心肌α,β和H_2受体以及电压依赖性钙通道引起 .     

哌(口替)啶对豚鼠气道神经功能的影响

渐增浓度的哌啶（０．０１～１．０μｍｏｌ／Ｌ１）抑制电场利激引起的豚鼠离体支气管内的胆碱能神经和感觉神经Ｃ纤维的兴奋作用,该作用可被纳洛酮阻断．哌啶不抑制卡巴可引起的支气管平滑肌收缩,也不抑制电场刺激引起的离体气管的松弛作用．说明哌啶通过μ阿片受体介导,具有抑制豚鼠气道内的兴奋性神经末梢的功能。     

K—Ⅱ和U—50488H对K阿片受体亲和力的比较

3,4-Dichloro-N-methyl-N-[trans-2-(1-delta 3-pyrrolinyl)-cyclohexyl] benzenacetamide hydrochloride (K-II) is a novel analogue of U-50488H. Previous studies have demonstrated that K-II is more potent than U-50488H in analgesic activity in mice and in inhibitory effect on electrically induced contractions of the isolated rabbit vas deferens. In this paper, we determined the affinities of K-II and U-50488H for kappa opiate receptor in guinea pig cerebellum and frontal cortex using radioreceptor binding assay (saturation studies and competition studies), and calculated Ki values of K-II and U-50488H by the Cheng-Prusoff equation. The results indicate that the affinity of K-II for kappa opiate receptor is 6-42 times greater than that of U-50488H. The selectivity of K-II for opiate receptor subtypes is being studied.     

K-Ⅱ和U-50488H对κ阿片受体亲和力的比较

3,4-二氯-N-甲基-N-[反式-2-(1-△³-吡咯啉基)环己基]苯乙酰胺(K-Ⅱ)是新合成的U-50488H类似物,其对小鼠的镇痛效应和对离体兔输精管的抑制作用均比U-50488H强。本文用放射受体结合试验方法对这两种化合物在富含x阿片受体的豚鼠小脑和大脑皮层前叶上的亲和力进行了比较,并求出这两种化合物的Ki值.结果表明K-Ⅱ对k阿片受体的亲和力比U-50488H强6～42倍。K-Ⅱ对阿片受体亚型选择性比较研究正在进行中。     

3H]U-69593 a highly selective ligand for the opioid kappa receptor

The selective kappa agonist U-50488 was recently discovered and characterized. In this study, the receptor binding properties of [3H]U-69593, an analog of U-50488, were characterized. [3H]U-69593 binds with high affinity (3 nM) to membranes prepared from guinea pig, mouse and rat brain. The number of kappa binding sites comprise only 13%, 9% and 4% of the total opioid sites, respectively. The benzmorphans, dynorphin, and compounds structurally related to U-50488 have high affinity for this kappa site.     

Effects of intracerebroventricularly administered mu-, delta- and kappa-opioid agonists on locomotor activity of the guinea pig and the pharmacology of the locomotor response to U50,488H.

The effects of intracerebroventricular administration of morphine, the selective mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO and DPDPE (total dose = 0.1, 1, 10, 100 nmol of each) produced piloerection and sedation, indicating that the responses of guinea pigs to mu- and delta-opioid agonists differed from those of rats and mice. In contrast, U50,488H (total dose = 10, 100 nmol) and dynorphin A(1-13) (total dose = 100 nmol) produced increased locomotor activity which was attenuated by pretreatment with naloxone and norbinaltorphimine, thus confirming the involvement of kappa-opioid receptors. Furthermore, pretreatment with spantide, baclofen, muscimol, bicuculline, MK-801, raclopride and atropine also inhibited the U50,488H-induced locomotor activity, suggesting the involvement of GABA, dopamine, excitatory amino acids, substance P and acetylcholine in this response.     

Antagonistic action of AA-2414 on thromboxane A2/prostaglandin endoperoxide receptor in platelets and blood vessels

AA-2414, (+/-)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoi c acid, inhibited the aggregation of guinea pig platelets induced by a prostaglandin endoperoxide (PGH2) analogue, U-44069 and the specific binding of another analogue, [3H]U-46619 to washed guinea pig platelets with IC50 values of 3.1 x 10(-7) and 8.2 x 10(-9) M, respectively. AA-2414 competitively inhibited the contraction of rabbit aorta and pig coronary arteries induced by U-44069 with pA2 values of 8.3 and 9.0, respectively. AA-2414 also inhibited the contraction of rabbit aorta induced by PGF2 alpha (pA2: 7.8) and the contraction of pig coronary arteries induced by PGF2 alpha, PGD2 and 9 alpha,11 beta-PGF2 with pA2 values of 7.8, 8.6 and 7.8, respectively. But, AA-2414 had no effect on the antiaggregatory effect of PGD2 on the aggregation of guinea pig platelets. In experiments with guinea pigs ex vivo, AA-2414 (0.1-1 mg/kg, p.o.) dose-dependently inhibited the platelet aggregation induced by U-44069; the inhibition at a dose of 1 mg/kg was 100% at 1 hr and was 89% even at 24 hr after the administration. The thromboxane (TX) A2/PGH2 receptor antagonistic action of AA-2414 was stereospecific. These results show that AA-2414 is a potent, orally active and long acting TXA2/PGH2 receptor antagonist. In addition, AA-2414 has PGF2 alpha, PGD2 and 9 alpha,11 beta-PGF2 antagonistic effects.     

P-7521--a new irreversible opioid ligand

In the receptor binding assay, P-7521 was a potent opioid ligand which acted mainly on mu receptor. The relative affinity ratio at mu, delta and kappa sites was 66:8:1. The inhibitory effects of P-7521 were 1868 and 6060 times more potent than morphine on the electrically evoked contractions in guinea pig ileum and mouse vas deferens, respectively and were readily antagonized by naloxone and Mr2266. These results indicate that P-7521 acted on mu receptor in guinea pig ileum and mouse vas deferens. In rabbit vas deferens, the compound had no agonist activity, but could antagonize the inhibitory effect of U-50488 H, a kappa agonist, showing the antagonistic characterization was on kappa receptor. The dissociation of P-7521 binding to opioid receptor were very difficult in mu binding assay and bioassays.