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KMID : 0811719980020030353
Korean Journal of Physiology & Pharmacology
1998 Volume.2 No. 3 p.353 ~ p.359
Inhibitory Effect of Caffeine on Carbachol-Induced Nonselective Cationic Current in Guinea-Pig Gastric Myocytes
Sung Joon Kim
Kyung Wan Min/Young Chul Kim/Sang Jin Lee/Insuk So/Ki Whan Kim
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[¥ãS] 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.
KEYWORD
Smooth muscle, Caffeine, Nonselective cationic current, Carbachol,
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