Inhibition of fundic strips from guinea-pig stomach: the effect of theophylline on the membrane potential, muscle contraction and ion fluxes.

The effect of theophylline on the smooth muscle cells of the fundic part of the stomach of the guinea pig was investigated. Theophylline hyperpolarized the membrane, inhibited spike discharges and slow waves and produced relaxation of the muscle cells. Furthermore, the theophylline-induced relaxation was not affected in low sodium solution or during inhibition of the sodium pump. Partial inhibition of the theophylline relaxation was seen in muscle depolarized by a high potassium solution and also when ATP was the relaxant. The potassium efflux was enhanced by ATP, but was not markedly changed by theophylline. A change in calcium efflux in the presence of theophylline could not be measured in quiescent preparations. The calcium influx was not changed by theophylline in Krebs, by low Ca, or by high K solution. Furthermore, the tissue content of cyclic AMP was increased by 59.6% in the presence of theophylline (2 x 10(-3) M). The conclusion is reached that the most likely mode of action of theophylline is a suppression of spontaneous activity and an extensive calcium binding to internal sites.