Muscarinic Receptors Controlling the Carbachol-Activated Nonselective Cationic Current in Guinea Pig Gastric Smooth Muscle Cells

The Japanese Journal of Pharmacology

Ki Whan Kim³  Tong Mook Kang¹  Myoung Kyu Park¹  Poong Lyul Rhee²  Dae Yong Uhm¹  Insuk So³  Jong Chul Rhee² 

[1] Department of Physiology,Sungkyunkwan University School of Medicine,Suwon 440-746,Korea;Department of Medicine Sungkyunkwan University School of Medicine,Suwon 440-746,Korea;Department of Physiology & Biophysics,Seoul National University College of Medicine,Seoul 110-799,Korea

关键词: Muscarinic receptor subtype;    Nonselective cationic current;    Carbachol;    Smooth muscle;   

DOI  :  10.1254/jjp.82.331

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(21)Cited-By(17)Muscarinic receptor subtypes controlling the nonselective cationic current in response to carbachol(ICCh)were studied in circular smooth muscle cells of the guinea pig gastric antrum using putative muscarinic agonists and antagonists.Both oxotremorine-M(an M2-selective agonist)and CCh dose-dependently activated the cationic current with EC50 values of 0.21±0.01μm and 0.97±0.06μM, respectively.In contrast, pilocarpine and McN-A 343(an M1-selective and a putative M4 agonist)were weak partial agonists.In response to 10μM CCh, 4-DAMP, methoctramine and pirenzepine dose-dependently inhibited ICCh and had IC50 values of 1.91±0.2nM, 0.46±0.07μM and 8.33±0.4μM, respectively.4-DAMP, methoctramine and pirenzepine shifted the concentration-response curves of ICCh to the right without significantly reducing the maximal current.Values of the apparent dissociation constant pA2 obtained from Schild plot analysis were 9.24, 7.72 and 6.62 for 4-DAMP, methoctramine and pirenzepine, respectively.Also, pertussis toxin completely blocked ICCh generation.These results suggest that the M2-subtype plays a crucial role in the activation of the ICCh, and a block of the M3-subtype reduces the sensitivity of the M2-mediated response with no significant reduction of maximum response.

【 授权许可】

Unknown