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Changes in VIP-related peptides after seizures in rat brain
NEUROPEPTIDES
IN NORMAL
AND PATHOLOGICAL
57
FUNCTION
of SP (9.3 + 1.2, n = 27) were unchanged in comparison to controls (VIP = 217 + 11, n = 34 and SP = 9.3 * 1.3, n = 26). Capsaicinpretreatment significantly reduced CGRP levels in the colonic tissue ( 38 f 2, n = 6, p < O.OS),while VIP and SP values were unchanged (VIP = 2 16 + 13, n = 6 and SP = 8.3 + 0.9, n = 6) as compared with controls. TNB-colitis induced in capsaicin-pretreated rats determined a marked reduction of tissue levels of all peptides: CGRP=6.7fl.l.n= 16;VIP=24.1+5.4,n= 10; SP= 1.1 j, 0.2, n = 16). Conclusions: The early and prolonged decrease of CGRP may be due to the release of peptide from intrinsic neurons and from capsaicin-sensitive afferents innervating the colonic tissue. The selective decrease of CGRP in the inflamed tissue of this model of colitis indicates the specific involvement of this peptide during the inflammatory process.
Impaired Balance of Antral Gastrin and Somatostatin Cells in Infants with Antral Gastrin Cell Hyperfunction G. Rindi*, B. Annibalet, M. Bonamicot, V. Corletot, G. Delle Favet and E. Solcia* *Pathologic Anatomy Unit, Dept. of Human Pathology, University of Pavia, Italy; tGastroenterology Unit and SPediatrics Unit, ‘La Sapienza’ University, Rome, Italy Six children presenting with gastrointestinal bleeding of unknown origin and variable symptoms have been analysed for gastrin-producing (G) cell function, acid secretion and were evaluated endoscopically and histologically for abnormality in the gastroduodenal mucosa. All patients showed elevated values of basal gastrinaemia (median 105 pg/ml [range 80-1401, vs normal median 50 pg/ml [25-80]), with abnormally increased peak values after meal (median 600 pg/ml [range 340-l 1201, vs normal median 200 [70-2851). Gastric secretion studies demonstrated elevated values of basal acid output (BAO) (median 0.1 mEq/Kg/h [range 0.06-0.281, vs normal median 0.04 [range 0.03-0.051) and peak acid output (PAO) (median 0.62 mEq/Kgih [range 0.6-0.71, vs normal median 0.41 [range 0.3-0.51). Circulating pepsinogen I was also evaluated revealing increased values (median 68 ng/ml [range 44-1741, vs normal median 34 [range 8661). Endoscopy showed duodenitis in all children and duodenal ulcer in three of them. Gastritis was observed in four cases, associated with Helicobacter Pylori colonisation in three of them. Quantitative analysis of antral gastrin-producing (G) and somatostatin-producing (D) cells revealed moderately, but significantly elevated figures of G cells (median 90 cell/linear mm of mucosa [range 83.1137.21, vs normal median 60.3 [range 49.2-80]), while D cells were at the lower reference limit (median 44.6 cell/linear mm of mucosa [range 29.3-47.21, vs normal median 53.5 [range 40-82.51). G/D cell ratio was
significantly elevated in all patients (median 2.55 [range 1.7-31, vs normal median 1.1 [range 0.59-21). These data indicate a diagnosis of antral gastrin cell hyperfimction (AGCH) associated with mild G cell hyperplasia and elevated G/D cell ratio and suggest a possible role of D cell deficit in the genesis of AGCH.
Changes in VIP-Related Peptides After Seizures in Rat Brain P. Romualdi, G. Lesa, A. Donatini and S. Ferri Dept. Pharmacology, University of Bologna, Imerio 48 - 40 126 Bologna, Italy Vasoactive Intestinal Polypeptide, VIP, (2) is present in high concentration in many areas of rat brain, particularly in cortical interneurons. We have recently shown that it is present as two major molecular forms: the entire VIP1 -28 and the newly identified heptapeptide VIP22-28 (1). We investigated a possible involvement of VIP-related peptides in seizures pharmacologically induced by pentylenetetrazole (PTZ) in the rat, since altered levels of different neuropeptides have been observed in rats with chemically or electrically-induced epilepsy. A detailed time course of VIP-related peptides’ changes was examined in rats administered with PTZ (45 mg/kg i.p., acutely or chronically). Tissues from rats sacrificed 5 min, 20 min, 24 h following PTZ injection or after 3 days of repeated treatment were assayed for VIP l-28 and VIP22-28 content. A specific antiserum recognizing the carboxy-terminus VIP22-28 was used. A marked decrease in total ir-VIP was observed 5 min after PTZ injection in cortex (78 vs 135 pmol/g tissue, p < O.OS), hypothalamus (10.6 vs 34.2, p < O.Ol), hippocampus (35 vs 57), striatum (7.1 vs 28.2, p < 0.01). midbrain (11.0 vs 26.8, p < 0.01) and medulla (5.7 vs 19.4, p < 0.01). Levels remained significantly lower at 20 min and were back to control values within 24 h. Levels detected in chronic treatment were: cortex 100.6 vs 135.0 pmol/g tissue; hypothalamus 43.8 vs 34.2, p < 0.05; hippocampus 50.7 vs 57.3; striatum 70.4 vs 28.2, p < 0.01; midbrain 30.9 vs 26.8 and medulla 16.8 vs 19.4 (Newman-Keuls test). Interestingly, concerning chromatographic characterization of ir-VIP, we observed a decrease of VIP1 -28 form and a corresponding increase of the smaller molecular form VIP22-28 in striatum, hippocampus and cortex of rats sacrificed 5 min, 20 min and also 24 h after PTZ. These results suggest that neurons containing VIPI28/VIP22-28 system are involved in PTZ-induced seizures, as reported for other neuropeptides. Further studies will elucidate a possible role for VIP-related peptides, namely VIP22-28, in this experimental condition. 1.
Romualdi, P., Rosenberger, J. G.. Gozzini, L. and Cox, B. M.
(1989). Peptides 10: 621-626. 2. Said,SandMutt,V.(1970).Science
169: 1217-1218.
IN NORMAL
AND PATHOLOGICAL
57
FUNCTION
of SP (9.3 + 1.2, n = 27) were unchanged in comparison to controls (VIP = 217 + 11, n = 34 and SP = 9.3 * 1.3, n = 26). Capsaicinpretreatment significantly reduced CGRP levels in the colonic tissue ( 38 f 2, n = 6, p < O.OS),while VIP and SP values were unchanged (VIP = 2 16 + 13, n = 6 and SP = 8.3 + 0.9, n = 6) as compared with controls. TNB-colitis induced in capsaicin-pretreated rats determined a marked reduction of tissue levels of all peptides: CGRP=6.7fl.l.n= 16;VIP=24.1+5.4,n= 10; SP= 1.1 j, 0.2, n = 16). Conclusions: The early and prolonged decrease of CGRP may be due to the release of peptide from intrinsic neurons and from capsaicin-sensitive afferents innervating the colonic tissue. The selective decrease of CGRP in the inflamed tissue of this model of colitis indicates the specific involvement of this peptide during the inflammatory process.
Impaired Balance of Antral Gastrin and Somatostatin Cells in Infants with Antral Gastrin Cell Hyperfunction G. Rindi*, B. Annibalet, M. Bonamicot, V. Corletot, G. Delle Favet and E. Solcia* *Pathologic Anatomy Unit, Dept. of Human Pathology, University of Pavia, Italy; tGastroenterology Unit and SPediatrics Unit, ‘La Sapienza’ University, Rome, Italy Six children presenting with gastrointestinal bleeding of unknown origin and variable symptoms have been analysed for gastrin-producing (G) cell function, acid secretion and were evaluated endoscopically and histologically for abnormality in the gastroduodenal mucosa. All patients showed elevated values of basal gastrinaemia (median 105 pg/ml [range 80-1401, vs normal median 50 pg/ml [25-80]), with abnormally increased peak values after meal (median 600 pg/ml [range 340-l 1201, vs normal median 200 [70-2851). Gastric secretion studies demonstrated elevated values of basal acid output (BAO) (median 0.1 mEq/Kg/h [range 0.06-0.281, vs normal median 0.04 [range 0.03-0.051) and peak acid output (PAO) (median 0.62 mEq/Kgih [range 0.6-0.71, vs normal median 0.41 [range 0.3-0.51). Circulating pepsinogen I was also evaluated revealing increased values (median 68 ng/ml [range 44-1741, vs normal median 34 [range 8661). Endoscopy showed duodenitis in all children and duodenal ulcer in three of them. Gastritis was observed in four cases, associated with Helicobacter Pylori colonisation in three of them. Quantitative analysis of antral gastrin-producing (G) and somatostatin-producing (D) cells revealed moderately, but significantly elevated figures of G cells (median 90 cell/linear mm of mucosa [range 83.1137.21, vs normal median 60.3 [range 49.2-80]), while D cells were at the lower reference limit (median 44.6 cell/linear mm of mucosa [range 29.3-47.21, vs normal median 53.5 [range 40-82.51). G/D cell ratio was
significantly elevated in all patients (median 2.55 [range 1.7-31, vs normal median 1.1 [range 0.59-21). These data indicate a diagnosis of antral gastrin cell hyperfimction (AGCH) associated with mild G cell hyperplasia and elevated G/D cell ratio and suggest a possible role of D cell deficit in the genesis of AGCH.
Changes in VIP-Related Peptides After Seizures in Rat Brain P. Romualdi, G. Lesa, A. Donatini and S. Ferri Dept. Pharmacology, University of Bologna, Imerio 48 - 40 126 Bologna, Italy Vasoactive Intestinal Polypeptide, VIP, (2) is present in high concentration in many areas of rat brain, particularly in cortical interneurons. We have recently shown that it is present as two major molecular forms: the entire VIP1 -28 and the newly identified heptapeptide VIP22-28 (1). We investigated a possible involvement of VIP-related peptides in seizures pharmacologically induced by pentylenetetrazole (PTZ) in the rat, since altered levels of different neuropeptides have been observed in rats with chemically or electrically-induced epilepsy. A detailed time course of VIP-related peptides’ changes was examined in rats administered with PTZ (45 mg/kg i.p., acutely or chronically). Tissues from rats sacrificed 5 min, 20 min, 24 h following PTZ injection or after 3 days of repeated treatment were assayed for VIP l-28 and VIP22-28 content. A specific antiserum recognizing the carboxy-terminus VIP22-28 was used. A marked decrease in total ir-VIP was observed 5 min after PTZ injection in cortex (78 vs 135 pmol/g tissue, p < O.OS), hypothalamus (10.6 vs 34.2, p < O.Ol), hippocampus (35 vs 57), striatum (7.1 vs 28.2, p < 0.01). midbrain (11.0 vs 26.8, p < 0.01) and medulla (5.7 vs 19.4, p < 0.01). Levels remained significantly lower at 20 min and were back to control values within 24 h. Levels detected in chronic treatment were: cortex 100.6 vs 135.0 pmol/g tissue; hypothalamus 43.8 vs 34.2, p < 0.05; hippocampus 50.7 vs 57.3; striatum 70.4 vs 28.2, p < 0.01; midbrain 30.9 vs 26.8 and medulla 16.8 vs 19.4 (Newman-Keuls test). Interestingly, concerning chromatographic characterization of ir-VIP, we observed a decrease of VIP1 -28 form and a corresponding increase of the smaller molecular form VIP22-28 in striatum, hippocampus and cortex of rats sacrificed 5 min, 20 min and also 24 h after PTZ. These results suggest that neurons containing VIPI28/VIP22-28 system are involved in PTZ-induced seizures, as reported for other neuropeptides. Further studies will elucidate a possible role for VIP-related peptides, namely VIP22-28, in this experimental condition. 1.
Romualdi, P., Rosenberger, J. G.. Gozzini, L. and Cox, B. M.
(1989). Peptides 10: 621-626. 2. Said,SandMutt,V.(1970).Science
169: 1217-1218.