Interaction between neurokinin A, VIP, prostanoids, and enteric nerves in regulation of duodenal function

Abstract

Neurokinin A (NKA) induces duodenal motility and increases mucosal permeability and bicarbonate secretion in the in situ perfused duodenum in anesthetized rats. In the present study, the NKA-induced increase in mucosal permeability was potentiated by luminal perfusion with lidocaine and diminished by vasoactive intestinal peptide (VIP) but unaltered by elevated intraluminal pressure. Elevation of intraluminal pressure, however, potentiated the stimulatory effect of NKA on bicarbonate secretion. In contrast, the tachykinin decreased the rate of alkalinization in rats subjected to elevated intraluminal pressure and treated with indomethacin. Similarly, NKA partially inhibited the VIP-stimulated bicarbonate secretion. Luminal lidocaine did not affect the secretory response to NKA. The motility induced by NKA was unaffected by VIP or lidocaine but decreased by elevated intraluminal pressure. It is concluded that the NKA-induced increase in duodenal mucosal bicarbonate secretion is independent of neurons and possibly mediated by prostanoids. The increase in mucosal permeability in response to NKA may be suppressed by mucosal nerves, perhaps utilizing VIP as one of the transmitters.

Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways

“…Although the majority of VIP is probably of neuronal origin, one cannot exclude the finding that VIP can also be released by other cells such as lymphocytes (21). Our results obtained after activation of human submucosal neurons are reinforced by an in vivo study showing that VIP was able to reduce the increase in paracellular permeability induced by substance P in the rat (14). VIP has also been reported to decrease transepithelial resistance in Caco-2 and HT29-Cl.19A cell lines (5).…”

“…Both in vivo or in vitro approaches have been employed in the few studies that have explored interactions between enteric neurons and the intestinal epithelial barrier. In vivo studies in animal models have suggested that neuromediators such as VIP, substance P, or acetylcholine are involved in the regulation of intestinal permeability (14,15,17). Although closely reproducing physiological conditions, these studies make difficult the accurate analysis of the regulatory mechanisms at cellular or molecular levels.…”

“…In addition, extrapolation of results from animal models to humans is often hazardous. In vitro studies performed on epithelial cell lines or whole mucosa/ submucosa have suggested that neuromediators can influence epithelial permeability (5,14). Nevertheless, these studies performed on reductionist models, while enabling description of the signaling pathways involved, do not take into account the complexity of cross talk between the epithelium and the underlying neuronal network.…”

Roles of Substance P Receptors in Human Colon Circular Muscle: Alterations in Diverticular Disease

“…In several tissues, including rat duodenum, there is evidence for tachykinin-prostaglandin interactions (Hallgren et al, 1998), but this did not seem to be the case in human sigmoid colon circular muscle. We found that a minor component of the contractile response was apparently due to Ach release, as in guinea pig ileum (Holzer and Lembeck, 1980), because responses to SP (but not to NKA) were slightly but significantly inhibited by atropine.…”

n–3 polyunsaturated fatty acids in the maternal diet modify the postnatal development of nervous regulation of intestinal permeability in piglets

“…In pigs, tetrodotoxin (TTX, a blocker of Na + channels) increased basal jejunal paracellular permeability suggesting that a basal neuronal activity exerts an inhibitory tonus on intestinal permeability (Hayden & Carey, 2000). In vivo studies in animal models suggested that different neuromediators participate in this regulation (Hällgren et al . 1998; Hayden & Carey, 2000).…”