Effects of phosphodiesterase inhibitors on spontaneous electrical activity (slow waves) in the guinea‐pig gastric muscle.

Abstract

1. The effects of the phosphodiesterase inhibitors caffeine, theophylline, isobutylmethylxanthine (IBMX) and rolipram on spontaneous electrical activity (slow waves) were studied in the circular muscle of the guinea‐pig gastric antrum. 2. All the inhibitors reduced slow wave frequency without changing the membrane potential and the slow wave configuration, but at higher concentrations they blocked the slow waves and caused membrane hyperpolarization. In the presence of the inhibitors a low level of irregular electrical activity could be observed in many preparations. 3. Isoprenaline, forskolin, dibutyryl cAMP and 8‐bromo‐cAMP all produced effects essentially similar to those of phosphodiesterase inhibitors. K+ (12 mM) and removal of K+ both depolarized the membrane and these were not affected by IBMX (1‐3 microM). A decrease in frequency caused by IBMX was also not significantly affected by 12 mM K+ or K+ removal and only partially antagonized by TEA or 4‐aminopyridine. 4. These results suggest that an increase in intracellular cAMP inhibits pacemaker activity of slow waves. An increase in K+ conductance does not seem to be a major factor in this inhibition. Slow waves appear to be a compound electrical activity in a group of muscle cells and are likely to be disintegrated by xanthine derivatives.

Unitary nature of regenerative potentials recorded from circular smooth muscle of guinea‐pig antrum

“…6). This occurred using lower concentrations than those found to be necessary to disrupt intracellular Ca¥ storage in other tissue, perhaps by phosphodiesterase inhibition (Tsuengo et al 1995) or by blocking the production of inositol trisphosphate (Toescu et al 1992). Whatever the case, the commonality of effects suggests that these three phenomena are in some way interrelated.…”

ET‐1‐associated vasomotion and vasospasm in lymphatic vessels of the guinea‐pig mesentery

“…The ET-1-induced enhancement of vasomotion was also blocked by caffeine. This could result through direct inhibition of IP 3 channels (Bezprozvanny et al, 1991), inhibition of PLC activity (Hamada et al, 1997) and/or phosphodiesterase-induced formation of cAMP (Beavo & Reifsnyder, 1990;Tsugeno et al, 1995). It did not occur through an action on RyRs, as RyRs while functionally present in the lymphatic smooth muscle did not abolish spontaneous or ET-1-induced vasomotion.…”

Identification of rhythmically active cells in guinea‐pig stomach

“…Subsequently the serosa and most of the longitudinal muscle was carefully removed under a dissecting microscope. In some experiments, preparations were attached at one end to a force transducer and held rigidly, serosal side up, at the other end (Tsuengo et al 1995). Intracellular recordings were made from a small area of smooth muscle, close to the point of rigid attachment, using conventional microelectrodes.…”