• Prof. dr. H.G. Gooszen, Dept Surgery, University Medical Center Utrecht.
• Prof. dr. J-P. Timmermans, Cell Biology and Histology, University of Antwerp, Belgium.
• Dr. A. Rijnierse and dr. A. Kraneveld, Div Pharmacology and Pathophysiology, UIPS, UU.

The aim of the project is the morphological, electrophysiological and neuropharmacological identification of the role, the mechanisms and the effects of the bi-directional interactions between the enteric nervous system and the enteric immune system on the functioning of the gastrointestinal tract under normal and inflammatory conditions.

Cellular electrophysiology and neuropharmacology using sharp and patch clamp microelectrode techniques for studying voltage-gated and ligand-gated ion channels and the excitability of neurons. Confocal laser scanning microscopy using fluorescent dyes for measurement of intracellular Ca2+ concentration. Immunohistochemistry with antibodies for identification of membrane receptors and cellular neuropeptides. Enteric neurons in wholemount preparations, cultured neurons, cell lines and primary cultured mast cells. Quantification of the integrity and permeability of the intestinal barrier in vitro in Ussing chambers.

Mast cells are often found in close proximity of sensory nerve endings in the intestine and there is a direct bi-directional communication between mast cells and the neurons. Intestinal inflammation has consequences for the functioning of the enteric nervous system, especially resulting from the activation of neurons by inflammatory mediators such as prostaglandines and interleukins. Alterations in this regulatory process, so as for instance occur during acute pancreatitis, food allergy and intoxication, can induce changes in permeability and integrity of the intestinal barrier.

Recent publications (for reprint requests mail to a.kroese@uu.nl):

Venneman, N.G., Petruzzelli, M., van Dijk, J.E., Verheem, A., Akkermans, L.M., Kroese, A.B., & van Erpecum, K.J. (2006) Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt-induced ileal mucosa injury. European Journal of Clinical Investigations, 36, 105-112.

Jørgensen, F., & Kroese, A.B. (2005) Ion channel regulation of the dynamical instability of the resting membrane potential in saccular hair cells of the green frog (Rana esculenta). Acta Physiologica Scandinavia, 185, 271-290.

De Jonge, F., De Laet, A., Van Nassauw, L., Brown, J.K., Miller, H.R., van Bogaert, P.P., Timmermans, J.P., & Kroese, A.B. (2004) In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation. American Journal of Physiology; Gastrointest Liver Physiol. 287, G178-191.

Kuo, J.J., Schonewille, M., Siddique, T., Schults, A.N., Fu, R., Bär, P.R., Anelli, R., Heckman, C.J, & Kroese, A.B. (2004) Hyperexcitability of cultured spinal motoneurons from presymptomatic ALS mice. Journal of Neurophysiology, 91, 571-575.

Rychter JW, van Minnen LP, Verheem A, Timmerman HM, Rijkers GT, Schipper MEI, Gooszen HG, Akkermans LMA, Kroese ABA. (2009) Pretreatment but not treatment with probiotics abolishes mouse intestinal barrier dysfunction in acute pancreatitis. Surgery, 145, 157-167