Inhibitory effect of caffeine on carbachol-induced nonselective cationic current in guinea-pig gastric myocytes.
- Author:
Sung Joon KIM
1
;
Kyung Wan MIN
;
Young Chul KIM
;
Sang Jin LEE
;
Insuk SO
;
Ki Whan KIM
Author Information
1. Department of Physiology & Biophysics, Seoul National University College of Medicine, Seoul 110-799, Korea.
- Publication Type:Original Article
- Keywords:
Smooth muscle;
Caffeine;
Nonselective cationic current;
Carbachol
- MeSH:
Caffeine*;
Carbachol;
Dialysis;
GTP-Binding Proteins;
Heparin;
Muscle Cells*;
Muscle, Smooth;
Receptors, Muscarinic
- From:The Korean Journal of Physiology and Pharmacology
1998;2(3):353-359
- CountryRepublic of Korea
- Language:English
-
Abstract:
In gastrointestinal smooth muscle, muscarinic stimulation by carbachol (CCh) activates nonselective cation channel current (ICCh) which is facilitated by intracellular (Ca2+) increase. Caffeine is widely used in experiments to mobilize Ca2+ from intracellular stores. This study shows a strong inhibitory effect of caffeine on ICCh in guinea-pig gastric myocyte. In this study, the underlying mechanism of the inhibitory effect of caffeine was investigated. ICCh was completely suppressed by the addition of caffeine (10 mM) to the superfusing solution. Inhibition of ICCh by caffeine was not related to the intracellular cAMP accumulation which was expected from the phosphodiesterase-inhibiting effect of caffeine. The blockade of InsP3-induced Ca2+ release by heparin had no significant effects on the activation of ICCh. When the same cationic current had been induced by intracellular dialysis of GTP(gammaS) in order to bypass the muscarinic receptor, the inhibitory effect of caffeine was significantly attenuated. The results of this study indicate that both intracellular signalling pathways for ICCh, proximal and distal to G-protein activation, are suppressed by caffeine. A major inhibition was observed at the proximal level.
