ATP通过P2受体调节大鼠近端结肠纵行肌的舒张与收缩反应(英文)

目的腺苷三磷酸(ATP)对大鼠离体远端结肠纵行肌运动的影响已明确,对近端结肠纵行肌的影响可能不同,但未有报告,为此对此进行观察并探讨其受体机制。方法观察静息张力时或预收缩时0.1μmol·L-1～1mmol·L-1ATP和1～100μmol·L-1腺苷对大鼠近端结肠纵行肌的抑制和兴奋作用。结果在静息张力下,1μmol·L-1～1mmol·L-1ATP对大鼠近端结肠纵行肌产生3种效应,即抑制自发性收缩反应,一过性轻度降低基础张力(0.05～0.08g),随后产生浓度依赖性收缩反应(0.04～0.44g)。0.1μmol·L-1河豚毒素不影响ATP的上述作用。在静息张力下,1～100μmol·L-1腺苷对近端结肠纵行肌未产生明显的收缩反应。应用5羟色胺(5HT)或乙酰胆碱(ACh)预收缩标本时,1μmol·L-1～1mmol·L-1ATP产生明显的浓度依赖性舒张反应(23.2%～94.6%,5HT预收缩;24.8%～92.4%,ACh预收缩),而腺苷引起的舒张反应明显小于ATP。结论在大鼠离体近端结肠纵行肌,ATP主要通过嘌呤嘧啶(P)2受体介导收缩反应,部分通过P1受体介导舒张反应。     

雷尼替丁和西咪替丁对大鼠结肠平滑肌条收缩活动的影响(英文)

通过大鼠离体结肠平滑肌条实验 ,观察雷尼替丁 ( 0 .0 2 ,0 .2 ,2和 10mmol·L- 1)和西咪替丁 ( 0 .0 .8和 4mmol·L- 1)对结肠收缩活动的影响 .结果表明 :雷尼替丁和西咪替丁增加结肠头端环行肌和结肠尾端纵行肌的平均收缩幅度以及结肠尾端环行肌的运动指数 ,减小结肠头端纵行肌的平均收缩幅度 ,并均有一定的剂量效应关系 ;雷尼替丁增加结肠头端纵行肌的静息张力和结肠尾端纵行肌的收缩频率 ,西咪替丁则降低结肠肌条的收缩频率 .阿托品( 0 .0 1μmol·L- 1)部分阻断雷尼替丁 ( 0 .2mmol·L- 1)对结肠肌条的兴奋作用 ,但不影响西咪替丁 ( 0 .8mmol·L- 1)的作用 ;六甲溴铵 ( 10 μmol·L- 1)不影响雷尼替丁和西咪替丁对结肠肌条的作用 .提示 ,雷尼替丁和西咪替丁对结肠肌条主要表现兴奋作用 ,雷尼替丁对结肠的作用与M受体有关     

多沙唑嗪对映体对大鼠离体心脏心肌活力的作用

目的观察多沙唑嗪(Dox)对映体对大鼠离体心房肌和心室肌功能的作用。方法制备大鼠离体左心房、右心房和右心室肌条标本。左右心房均分别累积给予Dox对映体3,10和30μmol·L-1。右心室非累积给予Dox对映体3,10和30μmol·L-1。测定心率和心肌收缩力。结果右旋Dox(R-Dox)3～10μmol·L-1,使28%的右心房(含窦房结)发生停搏反应,消旋Dox(rac-Dox)3～10μmol·L-1使7%的右心房(含窦房结)发生停博反应,左旋Dox(S-Dox)3～10μmol·L-1未诱发右心房(含窦房结)停搏反应。R-Dox3～30μmol·L-1随浓度增加,减慢大鼠离体右心房心率作用有增强趋势。rac-Dox 10和30μmol·L-1显著减慢大鼠离体右心房心率(P<0.01)。S-Dox 3～30μmol·L-1对大鼠离体右心房心率无影响。S-Dox 3～30μmol·L-1增强大鼠离体左心房心肌收缩。相反,R-Dox 3～30μmol·L-1浓度依赖性地抑制左心房心肌收缩(P<0.01)。rac-Dox 3～30μmol·L-1亦浓度依赖性地抑制左心房心肌收缩。S-Dox 3～30μmol·L-1对大鼠右心室肌收缩力无显著影响。R-Dox和rac-Dox 3～30μmol·L-1浓度依赖性地抑制右心室肌收缩(P<0.01)。结论 rac-Dox 3～10μmol·L-1可诱发大鼠离体心脏停搏,并显著抑制大鼠心室肌的收缩;rac-Dox对心脏的作用与R-Dox有关;同浓度的S-Dox对大鼠离体右心房心率无影响,对大鼠心室肌的收缩无作用。     

氯通道阻断剂对大鼠主动脉环收缩和舒张反应的影响

目的　观察氯通道阻断剂DIDS和呋塞米(furosemide)对苯肾上腺素 (phenylephrine,PHE)引起的收缩反应和ATP引起的内皮依赖性舒张效应的影响。方法　采用内皮完整和去内皮的大鼠离体主动脉环 ,进行等长张力实验。结果　DIDS(1～ 30 0 μmol·L-1)和furosemide(10～ 32 0μmol·L-1)均浓度依赖性抑制PHE引起的收缩反应 ,但对内皮完整的血管环抑制率和去内皮的血管环抑制率不同 ,DIDS的IC50 分别为 (12 0± 8 0 ) μmol·L-1和 (2 8 3± 7 3)μmol·L-1;furosemide的IC50 分别为 (17 9± 6 6 ) μmol·L-1和 (41 0± 15 6 ) μmol·L-1。DIDS(10 0 μmol·L-1)对 10μmol·L-1和 10 0 μmol·L-1的ATP舒张无影响 ,但可增加 1mmol·L-1ATP引起的舒张效应 (P <0 0 5 ) ;furosemide(2 0 0μmol·L-1)对 10 μmol·L-1的ATP舒张无影响 ,但可使 10 0μmol·L-1ATP和 1mmol·L-1ATP引起的舒张效应增强 (P<0 0 5 )。结论　DIDS和furosemide可抑制PHE引起的收缩 ,且对带内皮血管环的抑制率均大于去内皮血管环的抑制率 ,并可增加ATP引起的内皮依赖性舒张。     

催产素对大鼠离体胃平滑肌收缩活动的影响

观察催产素（ｏｘｙｔｏｃｉｎ）对大鼠胃不同部位肌条收缩活动的影响． 结果表明：１０ Ｕ·Ｌ－ １催产素可降低胃底纵行肌张力,升高胃体纵行肌,环行肌和胃窦纵行肌条的张力（升高百分率分别为８±８,３２±２０, ６±８）,增大胃体和胃窦各肌条的收缩波平均振幅及幽门环行肌的运动指数（增大百分率分别为２７±４１, ６２±３８, １２±１５, ３９±１９, ５３±２９）,增快幽门环行肌的收缩频率〔从（１．２±０．３）ｍ ｉｎ－ １ 增至（１．９±０．３） ｍ ｉｎ－ １〕;而１００ Ｕ·Ｌ－ １催产素升高胃体纵行肌和环行肌及胃窦纵行肌张力的同时降低其收缩波平均振幅,增快各肌条的收缩频率． 阿托品和六甲溴铵均不阻断催产素的上述作用． 结果表明催产素可能直接作用于平滑肌细胞,对大鼠离体胃平滑肌收缩活动起兴奋作用．     

腺苷及腺苷三磷酸对大鼠离体结肠平滑肌的作用

目的 比较腺苷和腺苷三磷酸对大鼠离体近端结肠纵行平滑肌活动的调节作用.方法 四导生理记录仪记录大鼠近端结肠纵行肌的等长舒张和收缩反应.结果 对于静息状态下的大鼠离体近端结肠纵行肌标本,腺苷无明显影响(P＞0.05).但是,腺苷三磷酸使静息状态下的大鼠离体近端结肠纵行肌产生微弱的舒张反应后续浓度依赖性收缩反应;腺苷三磷酸的上述作用不受神经阻断剂河豚毒素的影响.大鼠离体近端结肠纵行肌标本在五羟色胺或乙酰胆碱预收缩条件下,腺苷和腺苷三磷酸均可产生浓度依赖性舒张反应,但是腺苷引起的舒张反应明显弱于腺苷三磷酸(P＜0.01).结论 在大鼠离体近端结肠纵行肌,腺苷三磷酸可产生舒张反应和收缩反应,而腺苷仅产生舒张反应.     

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。     

P2Y受体介导大鼠胃体环行肌收缩反应的药理学特点

观察大鼠离体胃体环行肌和胃底环行肌不同的药理学特征，分析核苷及核苷酸类物质诱发胃体环行肌收缩反应的作用特点和受体机制。制备大鼠离体胃体环行肌和胃底环行肌标本，利用受体药理学技术观察药物诱发的收缩反应。在胃体环行肌KCl所致收缩反应与胃底环行肌无显著性差别；但是，CCh收缩胃体环行肌的EC₅₀值 [(0.45 ± 0.15) μmol·L⁻¹] 显著高于胃底环行肌 [(0.20 ± 0.09) μmol·L⁻¹, P < 0.01]。5-HT和His收缩两种标本的EC₅₀值无显著差异 (P > 0.05); 但是, 在胃体环行肌5-HT和His产生收缩反应的E_max值 [(0.81 ± 0.26) 和 (0.88 ± 0.27) g] 显著小于胃底环行肌 [(2.67 ± 0.61) 和 (1.90 ± 0.68) g, P < 0.01]。在预收缩胃体环行肌，ATP (0.1～3 000 μmol·L⁻¹) 诱发浓度依赖性收缩反应，未见舒张反应；在预收缩胃底环行肌标本，同浓度ATP诱发先舒张后收缩的双相反应，并呈浓度依赖性。ATP、UTP、ADP、2-MeSATP和α, β-MeATP浓度依赖性诱发大鼠胃体环行肌收缩反应，2-MeSATP的EC₅₀值为 (7.2 ± 5.2) nmol·L⁻¹比Ach [(3.47 ± 1.20) μmol·L⁻¹] 低500倍；各药物产生收缩反应的效价序列为：2-MeSATP>>ADP>ATP=UTP>α, β-MeATP>>腺苷。酚妥拉明、普萘洛尔、阿托品及河豚毒素不影响ATP和UTP诱发的胃体环行肌收缩反应。研究结果表明, 大鼠胃体环行肌的药理学特征明显不同于胃底环行肌; 核苷酸类物质通过某种特殊的P2Y受体介导胃体环行肌收缩反应，是调节胃体环行肌收缩功能的重要介质。
     

C型钠尿肽抑制大鼠胃窦环行肌自发性收缩活动

目的：研究钠尿肽对胃动力的作用及其可能的机制．方法：用四道记录仪记录胃窦环行肌条的自发性收缩活动;利用放射免疫技术测定cGMP的产生量;利用放射自显影技术分析钠尿肽受体在胃内的分布情况．结果：钠尿肽受体在大鼠胃的不同部位均有分布,但在胃窦部最多。ANP、BNP和CNP均能抑制胃窦环行肌条的自发性收缩,其中,CNP的作用尤为明显并呈剂量依赖关系．CNP的这种抑制性作用被鸟苷酸环化酶抑制剂LY83583所削弱,而用cGMF敏感的磷酸酯酶抑制剂zaparinist预处理时CNP的抑制作用明显增加．CNP明显提高胃窦环行肌cGMP的浓度．用非选择性钾通道阻断剂TEA预处理后发现CNP对胃窦环行肌自发性收缩活动的抑制作用明显减弱．结论：钠尿肽受体在大鼠的胃窦分布最多．CNP明显抑制大鼠胃窦环行肌的自发性收缩活动．CNP对大鼠胃窦环行肌自发性收缩活动的抑制效应是通过cGMP途径实现的．钾通道也参与CNP对大鼠胃窦平滑肌的舒张过程。     

格列本脲和亚甲蓝对缺氧诱发离体猪冠脉—过性舒张的影响

缺氧可诱发KC1 25 mmol·L~(-1)预收缩离体猪冠脉产生双相反应,先短暂(持续4.3±s0.8 min)舒张,随后持续收缩;除去内皮可消除缺氧诱发的冠脉舒张反应,并几乎完全消除收缩反应,格列本脲0.1,0.5,2.5和亚甲蓝5,10μmol·L~(-1)均可浓度依赖地抑制缺氧诱发的冠脉舒张反应;格列本脲2.5和亚甲蓝10μmol·L~(-1)合用可几乎完全消除此种舒张反应,提示缺氧诱发离体猪冠脉一过性舒张可能由ATP敏感性钾通道和内皮舒张因子(EDRF)共同中介。     

Inhibitory effect of dendroaspis natriuretic peptide on spontaneous contraction in gastric antral circular smooth muscles of guinea pigs

Aim： To determine whether the natriuretic peptide receptor （NPR） is present in the stomach of guinea pigs and to investigate the effect of dendroaspis natriuretic peptide （DNP） on the gastric motility of guinea pigs and its mechanism. Methods： The distribution of the NPR was analyzed by autoradioimmunography. The spontaneous contraction of gastric antral circular muscles of guinea pigs was recorded by a 4-channel physiograph. The whole cell patch-clamp technique was introduced to record calcium-activated potassium currents in the gastric myocytes isolated by collagenase. Results： The NPR existed in the gastric fundus, gastric body, and gastric antrum of guinea pigs, and its density was largest in the gastric antrum. DNP inhibited spontaneous contraction and exhibited a dose-dependent manner. The DNP-induced inhibition was diminished by LY83583 （a guanylate cyclase inhibitor） and was potentiated by zaprinast （a cGMP-sensitive phosphoesterase inhibitor）. The inhibitory effect of DNP on spontaneous contraction was also inhibited by tetraethylammonium （a non-selective potassium channel blocker）; 10 nmol/L DNP increased the calcium-activated potassium currents in the gastric circular myocytes of guinea pigs. Conelusion： The NPR is most common in the gastric antrum of guinea pigs. DNP significantly inhibits gastric motility in the gastric antrum of guinea pigs. The inhibitory effect occurs via a cGMP-dependent pathway, and a calcium-activated potassium channel may be also involved in the relaxation induced by DNP in gastric antral circular smooth muscles.     

On the ability of domperidone to selectively inhibit catecholamine-induced relaxation of circular smooth muscle of guinea-pig stomach

The effects of noradrenaline and dopamine, and their interactions with alpha- and beta-adrenoceptor antagonists and with domperidone, were studied on circular smooth muscle strips taken from the cardia, fundus, body and antrum of the guinea-pig stomach. Noradrenaline and dopamine caused relaxations of all tissues which were generally susceptible to antagonism by either propranolol or phentolamine in concentrations shown to antagonize the relaxations caused by isoprenaline or phenylephrine respectively. In addition, dopamine, in concentrations subthreshold for relaxation, caused contraction of the muscle strips which increased in intensity from the cardia to the antral region: these contractions were antagonized by phentolamine and yohimbine but were insensitive to prazosin: prazosin selectively inhibited the phenylephrine relaxations. With the exception of a modest reduction in the responses of the cardia to dopamine, all tissue responses to noradrenaline and dopamine were resistant to reserpine. Domperidone and haloperidol were found to selectively inhibit the phenylephrine- noradrenaline- and dopamine-induced relaxations of the stomach strips and to enhance the contractile component of dopamine's action: this ability of domperidone to facilitate a dopamine induced contraction, which was most marked in the body and antral regions, was prevented by phentolamine. It is thus concluded that domperidone antagonizes noradrenaline- and dopamine-induced relaxations at one adrenoceptor site having characteristics consistent with an alpha 1-adrenoceptor type whilst failing to antagonize at a further dopamine-sensitive adrenoceptor site involved in contraction of circular smooth muscle of the stomach and having characteristics consistent with an alpha 2-adrenoceptor.     

The effect of potassium on frog stomach muscle.

1 KCl relaxed strips of frog stomach muscle. Usually, the effect was biphasic, i.e. contraction followed by relaxation at a concentration of 137 mM. 2 The effect was mimicked by K2SO4. 3 Ouabain (5 and 10 micrograms/ml) blocked the relaxations and reversed them to contractions. The tension of strips was not affected. 4 Phenoxybenzamine (1 microgram/ml) and procaine (20 micrograms/ml) inhibited the relaxations, potentiated the contractile component and lowered the tone of the muscle. 5 The relaxation and the tone were inhibited by papaverine (5 micrograms/ml) but the contractile component was unaffected. 6 It is suggested that potassium-induced relaxations are mediated through the activation of the sodium pump.     

Ghrelin对急性胰腺炎大鼠胃肠动力的影响作用

目的从器官、组织的不同水平测定Ghrelin作用下急性胰腺炎大鼠胃肠动力的变化。方法应用牛磺胆酸钠经胆胰管逆行注射建立急性胰腺炎模型,造模前与造模后6 h分别尾静脉取血2 ml,测定血清淀粉酶、TNF-α、Il-6,再应用Ghrelin对给药组大鼠进行治疗,运用BD2000作为胃肠标记物,同时测定胃残留率和小肠推进比;多导生理仪记录大鼠胃窦肌电活动;多导生理仪记录离体大鼠胃体上1/3起搏区（带有ICC,interstitial cells of cajal的胃肌）和胃窦环行肌肌条收缩波改变。结果各组大鼠造模前与造模后6 h相比血清淀粉酶、TNF-α、Il-6明显升高,给药组大鼠胃残留量较对照组明显减少,给药组胃电慢波振幅及频率显著高于对照组,快波频率也增多,在组织水平,离体的动物胃体起搏区（带有ICC的胃肌）及胃窦环行平滑肌,在Ghre-lin作用下给药组肌条收缩幅度明显高于对照组;给药组胃体起搏区肌条的收缩频率与对照组无明显差别;给药组胃窦环行平滑肌条的收缩频率明显高于对照组,与其在体实验中胃排空明显增强,动力升高相吻合。结论Ghrelin能增强急性胰腺炎大鼠胃肠动力促进胃排空。     

Pharmacological characterization of 5-Hydroxytryptamine-receptor subtypes in circular muscle from the rat stomach

5-Hydroxytryptamine (5-HT) modulates gastric motility and gastric emptying via a variety of 5-HT receptor subtypes. However, regional and functional differences among 5-HT receptor subtypes in the rat stomach are not fully investigated. Thus, we aimed to characterize 5-HT receptor subtypes involved in the 5-HT-induced contractions in the isolated antral, corporal and fundic circular muscles of the rat stomach by measuring the contractile force. 5-HT induced concentration-dependent contractions in the antrum, corpus and fundus. 5-HT-induced antral contractions were partly blocked by atropine and enhanced by tetrodotoxin (TTX). Neither atropine nor TTX affected the corporal or the fundic contractions to 5-HT. In the antrum, 5-HT-induced contractions were inhibited by methysergide, tended to be inhibited by ketanserin, enhanced by SB-203186, but were not affected by WAY-100635, GR127935, RS-127445, ondansetron, or SB-269970. In the corpus, 5-HT-induced contractions were inhibited by ketanserin or methysergide. In the fundus, 5-HT-induced contractions were blocked by methysergide or RS-127445, but were enhanced by cinanserin or SB-203186. It is thus concluded that contractile responses to 5-HT in the antrum are mediated by 5-HT receptors on both smooth muscle and neurons whilst in the corpus and fundus responses are mainly mediated by 5-HT receptors on smooth muscle. Moreover, the antrum presents the contractile 5-HT2A and 5-HT2B receptors and the relaxant 5-HT4 receptors. The corpus presents the contractile 5-HT2A receptors, and the fundus presents the contractile 5-HT2B receptors and the relaxant 5-HT2A and 5-HT4 receptors.     

Participation of nitric oxide in the relaxation of the rat gastric corpus

Nitric oxide is an important mediator of the relaxation in the rat gastric fundus. The present study investigates the role of NO in the rat gastric corpus in vitro, since the corpus differs from the fundus with regard to its physiological function and its spontaneous motor behaviour.In the presence of guanethidine electrically induced relaxations of circular, mucosa-free corpus strips precontracted with bethanechol were concentration-dependently reduced by the NO-synthase inhibitors l-N^G-nitro-arginine (l-NNA) or l-N^G-nitro-argininemethyl-ester (l-NAME). The d-enantiomers were markedly less active. The inhibitory effect of l-NAME could be prevented by l-arginine. l-NNA and l-NAME, however, did not influence spontaneous motility or the bethanechol-induced contraction. Vasoactive intestinal polypeptide or sodium nitroprusside also relaxed the muscle strips, but these relaxations were not affected by l-NAME. When the corpus strips were stimulated electrically from baseline, they reacted with a contraction followed by relaxation. l-NNA or l-NAME blocked the relaxatory and enhanced the contractile component. In strips that also reacted with a rebound contraction, it was blunted by l-NAME. These effects of the NO-synthase inhibitors were abolished in the presence of atropine. Apamin increased the electrically induced contraction of the muscle strips. Inhibition of the relaxation together with a further shift to contraction could only be seen when apamin was combined with l-NNA. The inhibitory action of apamin and apamin + l-NNA was not influenced by atropine.The results demonstrate a role of NO in the relaxation of the circular muscle of the rat gastric corpus both at a postsynaptic site and via inhibition of acetylcholine release. The relaxation induced by vasoactive intestinal polypeptide does not involve NO.     

The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of action

Background and purpose:

The underlying mechanisms of gastric dysfunction during or after an episode of intestinal inflammation are poorly understood. This study investigated the effects of colitis on the contractile effects of motilin, an important endocrine regulator of gastric motility, in the antrum.

Experimental approach:

Myeloperoxidase (MPO) activity, NF-κB activity and motilin receptor density were determined in the antrum of rabbits 5 days after the induction of 2,4,6-trinitrobenzenesulphonic acid colitis. Smooth muscle and neural responses to motilin were studied in antral smooth muscle strips in vitro.

Key results:

Colitis did not affect MPO activity, but increased NF-κB activity in the antrum. Motilin receptor density in the antrum was not affected. Under control conditions, motilin induced a slowly developing tonic smooth muscle contraction. Five days post-inflammation, tonic contractions to motilin were reduced and preceded by a rapid initial contraction. Other kinases were recruited for the phosphorylation of myosin light chain (MLC) (a multi-functional MLC kinase), and for the inhibition of MLC phosphatase (Rho kinase in addition to protein kinase C) to mediate the motilin-induced contractions during inflammation. Colitis potentiated the cholinergic neural on-contractions in the antrum. This was associated with a hyper-reactivity to motilin and an increased muscle response to ACh.

Conclusions and implications:

Colitis altered the course of the motilin-induced smooth muscle contraction in the antrum. This involved changes in the kinases phosphorylating MLC. Increased cholinergic excitability to motilin in the antrum may play a role in the pathogenesis of inflammation-associated gastric motility disorders.