Quantitative Comparison of Growth-associated Protein-43 and Substance P in Ulcerative ColitisPälvi Ventoa, Tuula Kiviluotoa, Ulla Keränena, Heikki J. Järvinena, Eero Kivilaaksoa, and Seppo Soinilaba Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland b Department of Neurology and Institute of Biomedicine, University of Helsinki, Helsinki, Finland Correspondence to: Seppo Soinila, Dept. of Neurology, PO Box 300, 00029 HUS, Helsinki, Finland. E-mail: seppo.soinila@hus.fi The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis. Tissue samples from normal colon and regions of ulcerative colitis colon were obtained at surgery and immunostained for substance P, vasoactive intestinal polypeptide (VIP), somatostatin, calcitonin gene-related peptide (CGRP), enkephalin, galanin, GAP-43, and neuron-specific enolase (NSE). Visual examination and semiquantitative analysis revealed a clear increase in the immunoreactivity for substance P in ulcerative colitis, whereas no differences were observed in the distribution of the other peptides. Therefore, quantitative analysis was performed only for substance P immunoreactivity in the lamina propria, circular muscle layer, and myenteric ganglia. In the lamina propria, the score of total intensity of substance P immunoreactivity was 0.55 ± 0.15 (mean ± SEM) in normal colon, 1.30 ± 0.35 (p=0.087) in least affected colon, and 2.22 ± 0.28 (p<0.001) in moderately affected colon, whereas no significant differences were observed in immunoreactivities for GAP-43. Similar results were obtained for the mean substance P- or GAP-43-immunoreactive area. In the circular muscle layer, the number, density, total intensity, and perimeter of substance P- and GAP-43-immunoreactive fibers were essentially similar in normal colon, and in mild or moderately affected colon. We conclude that ulcerative colitis does not change the density of gut innervation as a whole. However, the density of substance P-containing nerves is specifically increased, probably due to increased peptide synthesis leading to better visibility of the fibers. (J Histochem Cytochem 49:749757, 2001) Key Words: GAP-43, substance P, quantitative morphometry, ulcerative colitis
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