The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum.
The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum.
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DOI：
10.1007/s00210-009-0434-8
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发表时间：
2009-10
影响因子：
3.6
通讯作者：
Ehlert, Frederick J.
中科院分区：
文献类型：
--
作者：
Griffin, Michael T.;Matsui, Minoru;Ostrom, Rennolds S.;Ehlert, Frederick J.
关键词：
我们探索了豚鼠回肠中的M2受体是否像M3受体基因敲除的小鼠一样，引起了高度有效的直接收缩反应。首先，我们从M受体基因敲除小鼠身上鉴定了4-DAMD芥末在回肠中的不可逆受体阻断活性，以验证其M3选择性。然后，我们使用4-湿芥末来灭活豚鼠回肠的M3反应，试图揭示直接的M2受体介导的收缩。在野生型、M2受体基因敲除和M3受体基因敲除小鼠中，M受体激动剂氧托莫林-M可引起强直的回肠收缩，其负对数EC50值(pEC50值)分别为6.75 ± 0.03、6.26 ± 0.05和6.99 ± 0.08。野生型和M2受体敲除小鼠的相应Emax值大致相同，但M3受体敲除小鼠的Emax仅为野生型的36%。在4-湿芥末处理后，野生型回肠中氧托莫林-M的量效曲线与M3基因敲除小鼠相似，其pEC50、Emax和选择性M受体拮抗剂的抑制作用相似。因此，4-湿芥末处理似乎选择性地使M3反应失活，并使野生型回肠的毒碱收缩行为类似于M3基因敲除小鼠的行为。在4-湿芥末处理后，豚鼠回肠对奥曲莫林-M的收缩反应表现出低效力和与M3反应一致的竞争-拮抗特征。因此，豚鼠回肠缺乏直接的、高效力的M2收缩成分，但可能有直接的、较低效力的M2成分。
We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of 6.75 ± 0.03, 6.26 ± 0.05, and 6.99 ± 0.08, respectively. The corresponding Emax values in wild-type and M2 receptor knockout mice were approximately the same, but that in the M3 receptor knockout mouse was only 36% of wild type. Following 4-DAMP mustard treatment, the concentration–response curve of oxotremorine-M in wild-type ileum resembled that of the M3 knockout mouse in terms of its pEC50, Emax, and inhibition by selective muscarinic antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M3 responses selectively and renders the muscarinic contractile behavior of the wild-type ileum similar to that of the M3 knockout mouse. Following 4-DAMP mustard treatment, the contractile response of the guinea pig ileum to oxotremorine-M exhibited low potency and a competitive-antagonism profile consistent with an M3 response. The guinea pig ileum, therefore, lacks a direct, highly potent, M2-contractile component but may have a direct, lower potency M2 component.
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影响因子：
5.8
作者：
Esqueda, EE;Gerstin, EH;Ehlert, FJ
通讯作者：
Ehlert, FJ
DOI：
10.1124/jpet.103.055327
发表时间：
2004-01-01
影响因子：
3.5
作者：
Griffin, MT;Matsui, M;Ehlert, FJ
通讯作者：
Ehlert, FJ
影响因子：
7.3
作者：
ROFFEL, AF;MEURS, H;ZAAGSMA, J
通讯作者：
ZAAGSMA, J
影响因子：
3.3
作者：
BARLOW, RB;SHEPHERD, MK;VEALE, MA
通讯作者：
VEALE, MA
影响因子：
5.8
作者：
KOTLIKOFF, MI;KUME, H;TOMASIC, M
通讯作者：
TOMASIC, M