Key result
Flufenamic acid (>10^-5 M) inhibited the amplitude and rate of rise of the upstroke phase of slow waves in guinea-pig stomach antrum circular smooth muscle cells, without altering their frequency.
Flufenamic acid selectively inhibits the second component of slow waves in guinea-pig gastric circular muscle, likely by inhibiting Ca2+-sensitive Cl- channels in intramuscular interstitial cells of Cajal.
Caution against clinical extrapolation from guinea-pig data; leaves open Cl- channel targeting in gastric ICC for future mechanistic studies.
The effects of flufenamic acid were investigated on slow waves, follower potentials and pacemaker potentials recorded respectively from circular smooth muscle cells, longitudinal smooth muscle cells and interstitial cells of Cajal distributed in the myenteric layers (ICC-MY) of the guinea-pig stomach antrum. Flufenamic acid (>10(-5) M) inhibited the amplitude and rate of rise of the upstroke phase of the slow waves, with no marked alteration in their frequency of occurrence. The inhibitory actions of flufenamic acid appeared to be mainly on slow potentials recorded from circular smooth muscle cells, but not on follower or pacemaker potentials. After abolishing spontaneous slow potentials with flufenamic acid, depolarizing current stimuli could evoke slow potentials with an amplitude that was much smaller than in the absence of flufenamic acid, with no significant alteration to the input resistance of the membrane. The time elapsed for the generation of the 2nd component of the slow waves or the slow potentials evoked during depolarizing current pulse stimulation was increased by flufenamic acid. The rate of rise of unitary potentials, but not the frequency of occurrence, was inhibited by flufenamic acid. These results indicate that the inhibitory actions of flufenamic acid appear to be mainly on the circular muscle layer including the interstitial cells of Cajal distributed within the muscle bundles (ICC-IM). Nifedipine-sensitive spike potentials were not inhibited by flufenamic acid. It is concluded that the selective inhibition of the 2nd component of slow waves by flufenamic acid may be mainly due to the inhibition of ion channels, possibly Ca2+-sensitive Cl--channels, activated during generation of slow potentials in the ICC-IM distributed in the circular muscle layer.
No takes yet. Share an insight, caveat, or question.
Hotta et al. (2005) studied Normal gastric smooth muscle (in vitro animal model). Flufenamic acid vs. Absence of flufenamic acid was evaluated on Amplitude and rate of rise of the upstroke phase of slow waves. Flufenamic acid (>10^-5 M) inhibited the amplitude and rate of rise of the upstroke phase of slow waves in guinea-pig stomach antrum circular smooth muscle cells, without altering their frequency.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: