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Am J Physiol Gastrointest Liver Physiol 276: G303-G310, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 1, G303-G310, January 1999

Region-specific antiproliferative effect of VIP and PACAP-(1---38) on rabbit enteric smooth muscle

Gert Van Assche1, Inge Depoortere1, Rita De Vos2, Karel Geboes2, Jozef J. Janssens1, Stephen M. Collins3, and Theo L. Peeters1

1 Center for Gastrointestinal Research and 2 Department of Morphology and Imaging, University of Louvain, B-3000 Louvain, Belgium; and 3 Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada L8N 3Z5

The ability of neuropeptides to modulate enteric smooth muscle proliferation was examined in primary explant cultures of rabbit gastric antrum and colon smooth muscle. Cell proliferation was determined by [3H]thymidine incorporation measurements and cell counting. Subcultured rabbit antrum and colon myocytes (passages 2-6) preserved a smooth muscle phenotype, as verified by immunohistochemistry for alpha -smooth muscle actin and electron microscopy. Both vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1---38) [PACAP-(1---38)] concentration dependently (10-10 to 10-6 M) inhibited the serum-induced [3H]thymidine incorporation [in colon, 48.2 ± 5.8 and 55.6 ± 9.3% of control with 10-6 M VIP and 10-7 M PACAP-(1---38)] and inhibited increase in cell numbers in cultures derived from the colon but not in those from the antrum. Effects of VIP and PACAP-(1---38) were mimicked by forskolin (10-7 to 10-6 M) but not by 8-bromo-cGMP, whereas theophylline enhanced the effects of VIP. Inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (10-3.5 M) did not alter the effects of VIP. Substance P, motilin, calcitonin gene-related peptide, and somatostatin had no effect. A single class of 125I-labeled VIP binding sites was found in antrum and colon myocyte cultures with an equal affinity for VIP and PACAP-(1---38) [dissociation constant (Kd) in antrum = 3.4 ± 0.8 nM for VIP and 2.0 ± 1.0 nM for PACAP-(1---38); Kd in colon = 2.0 ± 1.0 nM for VIP and 2.8 ± 1.6 nM for PACAP-(1---38)]. Density of binding sites in the antrum was higher than in the colon. In disease states such as inflammatory bowel disease, inhibition of myocyte proliferation by VIP and PACAP may serve to control smooth muscle hyperplasia in the colon but not in the antrum.

enteric neuropeptides; smooth muscle pathophysiology; signal transduction; neuropeptide receptors


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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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Neural regulation of intestinal smooth muscle growth in vitro
Am J Physiol Gastrointest Liver Physiol, September 1, 2000; 279(3): G511 - G519.
[Abstract] [Full Text] [PDF]


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