Prostaglandin regulation of gastric slow waves and peristalsis

Abstract

Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE(2) on slow waves in the murine stomach. PGE(2) increased slow-wave frequency, and this effect was mimicked by EP(3), but not by EP(2), receptor agonists. Chronotropic effects were due to EP(3) receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W(V) mice. Although the integrated chronotropic effects of EP(3) receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP(3) receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis.

Regulation of Gastric Electrical and Mechanical Activity by Cholinesterases in Mice

“…First-strand cDNA was prepared from RNA using oligo dT (12)(13)(14)(15)(16)(17)(18) seconds. PCR amplified fragments were sequenced to confirm the specificity of the primers.…”

“…The dominant contractile pattern of wild type stomachs was a continuous series of peristaltic contractions that began in the corpus and propagated to the pylorus. Video recordings were collected as previously described 18 using a high definition video camera (DMK31AF03, ImagingSource, Charlotte, NC, USA) connected to a computer using AstroIIDC software (ASC, Calgary, Alberta, Canada) to record QuickTime movies (.mov files) on a Mac OS-based computer (Mac, Apple Co, Cupertino, CA, USA). The tissues were constantly perfused with oxygenated KRB solution at 37°C.…”

“…Spatio-temporal maps (ST maps) were generated to measure the frequency, velocity and amplitude of peristaltic contractions and to characterize the pattern of motor activity, as previously described. 18,22 Briefly, images were thresholded to define the outer edges of the stomach which indented as contractile waves passed. The circumferential distance between the cut edges of the tissue was calculated and corresponding ST maps of diameter were generated.…”

“…5 We also tested selected application of neostigmine to the corpus and antrum regions of the muscle using a partitioned bath in which the 2 regions could be independently perfused. 18 Addition of neostigmine (1 M) to the corpus side of the partition increased slow wave frequency in both the corpus and antrum (from 6.2 ± 0.6 to 8.6 ± 0.6 cpm in the corpus and from 6.2 ± 0.6 to 8.6 ± 0.6 cpm in the antrum before and in the presence of neostigmine, respectively (n = 6; P < 0.05; data not shown). As with EFS, these data suggest that the antrum is able to be entrained by the corpus when the slow wave frequency in the dominant pacemaker area increases.…”

“…17 Inflammatory processes, including the generation of prostaglandins may also exert chronotropic effects and raise antral pacemaker frequency, breaking down the normal frequency gradient. 18 Acetylcholine (ACh), the dominant excitatory neurotransmitter in the GI tract, is released from enteric excitatory motor neurons. 1 ACh has ionotropic and chronotropic effects on gastric muscles, 19,20 and may increase slow wave amplitude and frequency and the fidelity of propagation in the post-prandial state.…”