Effects of the inflammatory mediator prostaglandin E2 on myenteric neurons in guinea pig ileum

Abstract

The effects of the inflammatory mediator prostaglandin E2 (PGE2) on myenteric neurons were investigated by intracellular recordings in a conventional plexus preparation. Bath application of PGE2 (1-1,000 nM) evoked a concentration-dependent and reversible slow depolarization and an augmentation of excitability in 23 of 26 AH and 12 of 13 S neurons. The amplitude of the slow depolarization ranged from 4 +/- 1 mV at 1 nM to 13 +/- 3 mV at 1 microM in S and AH neurons. In AH neurons, PGE2 evoked an increase in membrane resistance and a reduction of afterhyperpolarization. In S neurons, PGE2 evoked either an increase or a decrease in membrane resistance. PGE2 slightly reduced the amplitude of electrically evoked fast excitatory postsynaptic potentials and had no effect on slow excitatory postsynaptic potentials. Moreover, PGE2 evoked bursts of fast excitatory postsynaptic potentials and action potentials in S neurons, indicative of cyclical neural activity in the myenteric plexus. It is concluded that the inflammatory mediator PGE2 can act as an excitatory neuromodulator of gastrointestinal motility through direct action on neurons in the myenteric plexus.

Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon

“…We found that intraneuronal microelectrodes recorded excitatory responses (i.e., membrane depolarization and spike discharge) in submucosal ganglion cells in response to each of three different prostaglandins. The excitatory responses to each of these prostaglandins were similar to the responses to prostaglandin E 2 in myenteric neurons reported by others for guinea pig ileum (18). Unlike the prostaglandins, lubiprostone had no effect on the electrophysiology of the enteric neurons in the present study.…”

“…Prostaglandins D 2 , E 2 , F 2␣ , and I 2 are known stimulators of intestinal Cl Ϫ and bicarbonate secretion (5,20,21,34,43). These kinds of prostaglandinevoked secretory responses reflect interplay of actions on both epithelial cells and enteric neurons (18,30). Failure of TTX to suppress responses to lubiprostone suggests that it did not release prostaglandins to act on secretomotor neurons, nor did it act directly to stimulate the neurons.…”

Action of Bradykinin in the Submucosal Plexus of Guinea Pig Small Intestine

“…Members of the immune/inflammatory cell populations communicate with the ENS in paracrine manner through the release of chemical mediators (Frieling et al, 1994;Wood, 2002;Liu et al, 2003a). Exposure to the inflammatory mediators histamine, mast cell proteases, prostaglandins, leukotrienes, and cytokines modifies both neuronal excitability and neurotransmission (Nemeth et al, 1984;Frieling et al, 1994;Dekkers et al, 1997;Xia et al, 1999;Gao et al, 2002; Liu et al, 2003a,b).The present study was focused on bradykinin (BK) as one of the putative mediators formed during inflammatory, ischemic, and hemorrhagic states in the bowel (Zeitlin and Smith, 1973;Brown and Roberts, 2001). It was the second phase of a project to understand how BK formation might alter gut motility and secretion through actions in the ENS.…”

Effects of PGE2 in guinea pig colonic myenteric ganglia

“…A variety of immune-mediated inflammatory disorders exist, including Crohn's disease and ulcerative colitis, and dysmotility, hypersecretion, and enhanced perception of pain are common features (17,22,23,46). It is now clear that cutaneous and visceral inflammations lead to enhanced excitability of extrinsic primary afferent neurons and altered reflex activity (5,8,14,48). Changes may also occur in the afferent components of intrinsic enteric neural circuitry, and such changes could contribute to altered motor reflex activity in the inflamed bowel.…”

“…Within guinea pig submucosal plexus neurons in the colon, PGE 2 application has been shown to lead to membrane depolarization and increased action potential frequency, as well as increased chloride ion secretion (18). PGE 2 has also been shown to activate myenteric plexus neurons in the guinea pig ileum (14) and augment acetylcholine release from myenteric neurons of the small intestine (9,13) and colon (27,39). Moreover, in ileal myenteric AH cells, activation of adenylyl cyclase increases excitability by causing a membrane depolarization and suppression of the prolonged afterhyperpolarization (45), consistent with the known effects of Trichinella-induced inflammation in the small intestine (44).…”