Jong Chul Rhee1, Poong Lyul Rhee1, Myoung Kyu Park2,
Insuk So3, Dae Yong Uhm2,
Ki Whan Kim3 and Tong Mook Kang2,*
1Departmentﾊof Medicine and 2Department of Physiology,
Sungkyunkwan University School of Medicine, Suwon 440-746, Korea
3Departmentﾊof Physiology & Biophysics, Seoul National University
College of Medicine, Seoul 110-799, Korea
*ﾊTo whom correspondence should be addressed.
Abstract: 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ﾊｱﾊ0.01ﾊmm
and 0.97ﾊｱﾊ0.06ﾊmM,
respectively. In contrast, pilocarpine and McN-Aﾊ343 (an M1-selective
and a putative M4ﾊagonist) were weak partial agonists. In response
to 10ﾊmM CCh, 4-DAMP, methoctramine and pirenzepine
dose-dependently inhibited ICCh and had IC50
values of 1.91ﾊｱﾊ0.2ﾊnM, 0.46ﾊｱﾊ0.07ﾊmM
and 8.33ﾊｱﾊ0.4ﾊmM,
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.
Keywords: Muscarinic receptor subtype, Nonselective cationic current,
Carbachol, Smooth muscle