Five subtypes of muscarinic receptors are expressed in gastric smooth muscles of guinea pig.
- Author:
Insuk SO
1
;
Dong Ki YANG
;
Hyun Jin KIM
;
Kyung Wan MIN
;
Tong Mook KANG
;
Sung Joon KIM
;
Ki Whan KIM
;
Ki Ho PARK
;
Ju Hong JEON
;
Kyung Ho CHOI
;
In Gyu KIM
Author Information
1. Department of Physiology, College of Medicine, Seoul National University, Seoul 110-799, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
guinea pigs;
muscle contraction;
nonselec-tive cation channel;
receptors;
muscarinic;
stomach
- MeSH:
Animals;
Base Sequence;
Carbachol/pharmacology;
Cations;
Cholinergic Agonists/pharmacology;
Dose-Response Relationship, Drug;
Drug Interactions;
Guinea Pigs;
Ion Channels/drug effects/metabolism/physiology;
Muscarinic Antagonists/pharmacology;
Muscle Contraction/drug effects;
Muscle, Smooth/drug effects/*metabolism;
Piperidines/pharmacology;
Receptors, Muscarinic/chemistry/classification/*metabolism;
Stomach/drug effects/*metabolism
- From:Experimental & Molecular Medicine
2003;35(1):46-52
- CountryRepublic of Korea
- Language:English
-
Abstract:
Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. In this study, the nonselective cation channel activated by carbachol (ICCh) was examined in circular smooth muscle cells of the guinea pig gastric antrum using patch-clamp technique. 4-DAMP inhibited ICCh dose- dependently with IC50 of 1.1 +/- 0.1 nM (n = 6). GTPgS- induced current, however, was not inhibited by 10 nM 4-DAMP. ICCh was not recorded in pertussis- toxin (PTX)-pretreated smooth muscle cells of gastric antrum. ICCh values in response to 10 mM CCh at a holding potential of 60 mV were -330 32 pA (n=4) and -15 +/- 3 pA (n = 6) in the control and PTX-treated cells, respectively (P<0.01). Sensitivities to nanomolar 4-DAMP and PTX suggest the possible involvement of m4 subtype. Using sequence information obtained from cloned guinea pig muscarinic receptor genes, it is possible to amplify the cDNAs encoding m1-m5 from guinea pig brain tissue. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptor were present in circular smooth muscle cells of the guinea pig gastric antrum. Together with our previous results showing that Go protein is important for activation of ACh-activated NSC channels, our results suggest that ICCh might be activated by acetylcholine through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach.
