Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions.

Subtypes of muscarinic receptors regulating gallbladder cholinergic contractions.
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调节胆囊胆碱能收缩的毒蕈碱受体亚型。

DOI:
10.1152/ajpgi.1999.276.5.g1243
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发表时间:
1999
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Ryan,JP
Ryan,JP
中科院分区:
--
文献类型:
--
作者:
Parkman,HP;Pagano,AP;Ryan,JP

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本研究的目的是确定毒蕈碱受体亚型调节胆囊胆碱能收缩的功能作用。电场刺激(EFS; 16 Hz)可引起豚鼠胆囊肌条的收缩反应,1 μM河豚毒素(对照组的2 ± 2%)和1 μM阿托品(对照组的1 ± 1%)可抑制这种收缩反应,表明内源性胆碱能神经被激活。外源性ACh(5 μM)诱导的收缩被阿托品(对照的1 ± 1%)抑制,但不被河豚毒素(对照的102 ± 1%)抑制,表明对平滑肌有直接作用。M1受体拮抗剂哌仑西平(10 nM)对乙酰胆碱诱导的收缩无影响,但可抑制EFS诱导的收缩11 ± 3%。M2受体拮抗剂methoctramine(10 nM)对乙酰胆碱诱导的收缩无影响,但可使EFS诱导的收缩增加5 ± 2%。M3拮抗剂4-DAMP(10 nM)抑制ACh诱导的收缩14 ± 4%,抑制EFs诱导的收缩22 ± 5%。结论:特异性M1、M2和M3受体通过调节胆碱能神经释放ACh并介导胆囊肌收缩来调节胆囊肌收缩。胆碱能收缩由平滑肌上的M3受体直接介导。M2受体位于胆碱能神经上,作为连接前抑制性自身受体发挥功能。M1受体位于胆碱能神经上,作为连接前易化性自身受体发挥功能。
The aim of this study was to determine the functional role of muscarinic receptor subtypes regulating gallbladder cholinergic contractions. Electrical field stimulation (EFS; 16 Hz) produced contractile responses of guinea pig gallbladder muscle strips in vitro that were inhibited by 1 μM tetrodotoxin (2 ± 2% of control) and 1 μM atropine (1 ± 1% of control), indicating activation of intrinsic cholinergic nerves. Exogenous ACh (5 μM)-induced contractions were inhibited by atropine (1 ± 1% of control) but not tetrodotoxin (102 ± 1% of control), indicating a direct effect on smooth muscle. The M1receptor antagonist pirenzepine (10 nM) had no effect on ACh-induced contractions but inhibited EFS-induced contractions by 11 ± 3%. The M2antagonist methoctramine (10 nM) had no effect on ACh-induced contractions but augmented EFS-induced contractions by 5 ± 2%. The M3antagonist 4-DAMP (10 nM) inhibited ACh-induced contractions by 14 ± 4% and EFS-induced contractions by 22 ± 5%. In conclusion, specific M1, M2, and M3receptors modulate gallbladder muscle contractions by regulating ACh release from cholinergic nerves and mediating the contraction. Cholinergic contractions are mediated by M3receptors directly on the smooth muscle. M2receptors are on cholinergic nerves and function as prejunctional inhibitory autoreceptors. M1receptors are on cholinergic nerves and function as prejunctional facilitatory autoreceptors.
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