Potentiation of carbachol-induced detrusor smooth muscle contractions by beta-adrenoceptor activation.
Potentiation of carbachol-induced detrusor smooth muscle contractions by beta-adrenoceptor activation.
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DOI：
10.1016/j.ejphar.2009.01.034
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发表时间：
2009-03-15
影响因子：
5
通讯作者：
Ratz PH
中科院分区：
文献类型：
--
作者：
Klausner AP;Rourke KF;Miner AS;Ratz PH
在不含尿激酶的兔膀胱条中，β-肾上腺素受体激动剂异丙肾上腺素显著降低基础逼尿肌平滑肌张力，并抑制低浓度毒蕈碱受体激动剂卡巴胆碱产生的收缩。在卡巴胆碱浓度-反应曲线中，异丙肾上腺素不是抑制，而是加强高卡巴胆碱浓度产生的收缩。因此，卡巴胆碱浓度-反应曲线被异丙肾上腺素从浅的分级关系移动到陡峭的开关样关系。酪氨酸激酶抑制剂，染料木素，抑制卡巴胆碱诱导的收缩只有在异丙肾上腺素的存在。由单一高浓度卡巴胆碱（1 µM）产生的收缩显示出1个快峰和1个慢峰。在异丙肾上腺素的存在下，慢峰没有加强，但延迟，和U-0126（丝裂原活化蛋白激酶激酶抑制剂）选择性抑制这种延迟伴随细胞外信号调节激酶（ERK）磷酸化的抑制。异丙肾上腺素减少ERK磷酸化只有在卡巴胆碱的情况下。这些数据支持这样的概念，即通过抑制弱收缩，增强强收缩，并产生更像开关的浓度-反应曲线，β-肾上腺素受体刺激增强了毒蕈碱受体诱导的逼尿肌平滑肌收缩的有效性。此外，β-肾上腺素受体刺激改变了卡巴胆碱产生收缩的细胞机制。讨论了多受体和多细胞串扰的潜在意义。
In strips of rabbit bladder free of urothelium, the β-adrenoceptor agonist, isoproterenol, significantly reduced basal detrusor smooth muscle tone and inhibited contractions produced by low concentrations of the muscarinic receptor agonist, carbachol. During a carbachol concentration-response curve, instead of inhibiting, isoproterenol strengthened contractions produced by high carbachol concentrations. Thus, the carbachol concentration-response curve was shifted by isoproterenol from a shallow, graded relationship, to a steep, switch-like relationship. The tyrosine kinase inhibitor, genistein, inhibited carbachol-induced contractions only in the presence of isoproterenol. Contraction produced by a single high carbachol concentration (1 µM) displayed 1 fast and 1 slow peak. In the presence of isoproterenol, the slow peak was not strengthened, but was delayed, and U-0126 (mitogen-activated protein kinase kinase inhibitor) selectively inhibited this delay concomitantly with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation. Isoproterenol reduced ERK phosphorylation only in the absence of carbachol. These data support the concept that, by inhibiting weak contractions, potentiating strong contractions, and producing a more switch-like concentration-response curve, β-adrenoceptor stimulation enhanced the effectiveness of muscarinic receptor-induced detrusor smooth muscle contraction. Moreover, β-adrenoceptor stimulation changed the cellular mechanism by which carbachol produced contraction. The potential significance of multi-receptor and multi-cell crosstalk is discussed.
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影响因子：
7.3
作者：
FUKUMITSU, T;HAYASHI, H;TOMITA, T
通讯作者：
TOMITA, T
DOI：
10.1111/j.1748-1716.1995.tb09945.x
发表时间：
1995-09-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
KHADRA, MH;SATCHELL, PM;VAUGHAN, CW
通讯作者：
VAUGHAN, CW
影响因子：
5.3
作者：
Dumaz, N;Light, Y;Marais, R
通讯作者：
Marais, R
影响因子：
3.6
作者：
Berkeley, JL;Levey, AI
通讯作者：
Levey, AI
影响因子：
13.8
作者：
Ferrell, JE
通讯作者：
Ferrell, JE