Inhibitory Effect of Caffeine on Carbachol-Induced Nonselective Cationic Current in Guinea-Pig Gastric Myocytes

Inhibitory Effect of Caffeine on Carbachol-Induced Nonselective Cationic Current in Guinea-Pig Gastric Myocytes

<P> In gastrointestinal smooth muscle, muscarinic stimulation by carbachol (CCh) activates nonselective cation channel current (I<SUB>CCh</SUB>) which is facilitated by intracellular [Ca<SUP>2&#8290;</SUP>] increase. Caffeine is widely used in experiments to mobilize Ca<SUP>2&#8290;</SUP> from intracellular stores. This study shows a strong inhibitory effect of caffeine on I<SUB>CCh</SUB> in guinea-pig gastric myocyte. In this study, the underlying mechanism of the inhibitory effect of caffeine was investigated. I<SUB>CCh</SUB> was completely suppressed by the addition of caffeine (10 mM) to the superfusing solution. Inhibition of I<SUB>CCh</SUB> by caffeine was not related to the intracellular cAMP accumulation which was expected from the phosphodiesterase-inhibiting effect of caffeine. The blockade of InsP<SUB>3</SUB>-induced Ca<SUP>2&#8290;</SUP> release by heparin had no significant effects on the activation of I<SUB>CCh</SUB>. When the same cationic current had been induced by intracellular dialysis of GTP[γS] 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 I<SUB>CCh</SUB>, proximal and distal to G-protein activation, are suppressed by caffeine. A major inhibition was observed at the proximal level.