Open AccessMuscarinic Receptors Controlling the Carbachol-Activated Nonselective Cationic Current in Guinea Pig Gastric Smooth Muscle Cells
Author(s) -
Jong Chul Rhee,
PoongLyul Rhee,
Myoung Kyu Park,
Insuk So,
Dae Yong Uhm,
Ki Whan Kim,
Tong Mook Kang
Publication year - 2000
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.82.331
Subject(s) - methoctramine , pirenzepine , carbachol , muscarinic acetylcholine receptor , endocrinology , medicine , schild regression , agonist , chemistry , oxotremorine , pilocarpine , muscarinic acetylcholine receptor m3 , receptor , biology , neuroscience , epilepsy
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 +/- 0.01 microm and 0.97 +/- 0.06 microM, respectively. In contrast, pilocarpine and McN-A 343 (an M1-selective and a putative M4 agonist) were weak partial agonists. In response to 10/microM CCh, 4-DAMP, methoctramine and pirenzepine dose-dependently inhibited ICCh and had IC50 values of 1.91 +/- 0.2 nM, 0.46 +/- 0.07 microM and 8.33 +/- 0.4 microM, 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.