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NEUROREGULATION AND MOTILITY

Prostaglandin regulation of gastric slow waves and peristalsis

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada

Submitted 26 December 2008 ; accepted in final form 1 April 2009

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 PGE₂ on slow waves in the murine stomach. PGE₂ increased slow-wave frequency, and this effect was mimicked by EP₃, but not by EP₂, receptor agonists. Chronotropic effects were due to EP₃ 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 EP₃ 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. EP₃ 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.

interstitial cells of Cajal; EP receptor; gastroparesis; pacemaker; tachygastria