Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats  

作　　者：HelenaFWrzos TarunTandon AnnOuyang 

机构地区：[1]DivisionofGastroenterologyandHepatology,DepartmentofMedicine,CollegeofMedicine,PennsylvaniaStateUniversity,USA

出　　处：《World Journal of Gastroenterology》2004年第22期3292-3298,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by NIH-grant ROI-DK-34148

摘　　要：AIM:To investigate the pathway(s)mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent,bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS:Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer.Isometric tension was recorded.Cumulative concentration-response curves were obtained for(+)-cis- dioxolane(cD),a nonspecific muscarinic agonist,at 10^(-8)- 10^(-4)mol/L,in the presence of tetrodotoxin(TTX,10^(-7)mol/L). Results were normalized to cross sectional area.A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1(pirenzepine), M2(methoctramine)and M3(darifenadn)muscarinic receptor subtypes.The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment.The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS:A dose-dependent contractile response observed with bethanechol,was not affected by TTx.The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol.Lack of calcium as well as the presence of the L-type calcium channel blocker,nifedipine,also inhibited the cholinergic contraction,with a reduction in response from 2.5±0.4 g/mm^2 to 1.2±0.4 g/mm^2(P<0.05).The dose- response curves were shifted to the right by muscarinic antagonists in the following order of affinity:darifenacin (M_3)>methocramine(M_2)>pirenzepine(M_1). CONCLUSION:The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s)involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels.The presence of the residual contractile response after the treatment with nifedipine,suggesAIM: To investigate the pathway (s) mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent, bebhanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS: Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer. Isometric tension was recorded. Cumulative concentration-response curves were obtained for (+)-cisdioxolane (cD), a nonspecific muscarinic agonist, at 10^-8-10^-4mol/L, in the presence of tetrodotoxin (TTX, 10^-7mol/L). Results were normalized to cross sectional area. A repeat concentration-response curve was obtained after incubation of the muscle for 90min wibh antagonists for M1(pirenzepine), M2(methoctramine) and M3(darifenacin) muscarinic receptor subtypes. The sensitivity to PTX was tested by the ip injection of 100mg/kg of PTX 5d before the experiment. The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS: A dose-dependent contractile response observed with bethanechol, was not affected by TTX. The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol. Lack of calcium as well as the presence of the L-type calcium channel blocker, nifedipine, also inhibited the cholinergic contraction, with a reduction in responsefrom 2.5±0.4g/mm^2 to 1.2±0.4g/mm^2(P<0.05), The doseresponse curves were shifted to the right by muscarinic antagonists in the following order of affinity: darifenacin (M3)>methocramine (M2)>pirenzepine (M1). CONCLUSION: The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pabhway(s) involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels. The presence of the residual contractile response after the treatment with nif

关 键 词：Anesthetics  Local Animals BENZOFURANS BETHANECHOL Calcium Calcium Channel Blockers Cholinergic Agonists Dose-Response Relationship  Drug GTP-Binding Proteins In Vitro Male Muscarinic Antagonists Muscle Contraction Muscle  Smooth Nifedipine Pertussis Toxin Pirenzepine Pyloric Antrum PYRROLIDINES RATS Rats  Sprague-Dawley Receptor  Muscarinic M1 inhibitors Receptor  Muscarinic M2 Receptor  Muscarinic M3 Signal Transduction Tetrodotoxin 

分 类 号：R337.2[医药卫生—人体生理学]