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We describe here a depletion of peptide containing nerves and cells in Hirschsprung's disease, in comparison with specimens of bowel taken from age-matched neonates with no evidence of chronic constipation. VIP content in the diseased specimens was reduced by almost 80%, from 110/+-10.6 (mean +/- SEM) pmol VIP/g wet weight of tissue in controls to 23.8 +/- 3.5 pmol/g in the mid-portion of the diseased specimens. In addition, the numbers of enteroglucagon and somatostatin cells in the mucosa were significantly reduced in the aganglionic portions. Enteroglucagon cells were reduced from 55 +/- 7 in controls to 27 +/- 2 in proximal portions rising to 44 +/- 3 and 49 +/- 4 cells/mm2 in middle and distal areas. Somatostatin cell numbers also fell, from 5.5 +/- 1.9 to 1.8 +/- 0.8, 2.5 +/- 0.7 and 3.8 +/- 0.9 cells/mm2 in similar areas. Further investigation of the abnormalities of the diffuse neuroendocrine system in Hirschsprung's disease may help in understanding the nature of this condition and provide additional information on the role of these peptides in the control of gut function.
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PMID:Abnormalities of the colonic regulatory peptides in Hirschsprung's disease. 617 58

VIP- and substance P-like immunoreactivities were found in considerable concentrations (VIP: 17.3 +/- 4.8 pmol/g, mean +/- SEM; substance P:11.1 +/- 1.8 pmol/g) in the uveal portion of the guinea pig eye. Immunocytochemistry localised these two regulatory peptides to nerve fibres found principally in a plexus in the iris (substance P) and in an extensive network surrounding the blood vessels of the choroid (VIP). A remarkable anatomical demarcation of the two types of peptide-containing nerves was established by the staining of substance P-containing nerves, which stops at the level of the ciliary body. This uveal area is known to be involved in the ocular responses to nociceptive stimuli. At the ultrastructural level, immunoreactivity for both peptides was localised to distinct subpopulations of p-type nerves, distinguishable by the size of their large dense-cored vesicles. Those immunoreactive for VIP were significantly larger (p less than 0.0005) than those immunoreactive for substance P (95 +/- 7 nm and 82 +/- 9 nm respectively; mean +/- SD). Interruption of the trigeminal pathway produced a remarkable decrease of substance P immunoreactivity in the anterior portion of the uvea (9.1 +/- 1.5 pmol/g, mean +/- SEM, control; 5.3 +/- 1.3 pmol/g, denervated), but not of VIP immunoreactivity in the choroid. Following colchicine treatment, VIP-immunoreactive neuronal cell bodies were localised in the choroid. The separate anatomical localisations and distributions of the two uveal peptides appear to be related to their different origins and functional roles in the response of the eye to noxious stimuli.
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PMID:Mapping, quantitative distribution and origin of substance p- and VIP-containing nerves in the uvea of guinea pig eye. 618 41

In recent years, distinct changes in regulatory peptides have been found in a number of gastrointestinal diseases. Grass sickness is a fatal disease of horses for which the etiology has yet to be fully ascertained. In this study, the peptide-containing nerves and ganglionic and mucosal endocrine cells of the ileum, colon and rectum were investigated in horses with sub-acute or chronic grass sickness and compared with normal controls using immunocytochemistry, at both the light and electron microscopical levels, and radioimmunoassay. A substantial loss of both peptide-containing cells and nerves was found in all of the sick horses, particularly in the ileum. Electron microscopy revealed marked degeneration of nerves in the gut wall. Fibers containing granules immunostained for substance P or VIP, using the immunogold staining technique, underwent extensive degranulation in grass sickness, with the formation of multiple vacuoles. Radioimmunoassay of peptide content also showed that the most drastic changes occurred in the ileum. For example, VIP content was significantly reduced from 109 +/- 19.8 (mean +/- SEM) pmoles/g in controls to 6.8 +/- 1.4 pmoles/g in grass sickness (p less than 0.001) and substance P from 65.9 +/- 8.1 to 31.3 +/- 9.5 (p less than 0.02). These results may have applications in the diagnosis and treatment of grass sickness.
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PMID:The regulatory peptide system of the large bowel in equine grass sickness. 620 92

The report of a significant increase in plasma VIP concentration (PVC) during endoscopy of the upper gastrointestinal tract prompted us to examine this question under comparable experimental conditions, with simultaneous determination of serum gastrin concentration (SGC). Thirteen patients took part in a study wherein PVC and SGC were determined before, during and after oesophagogastroduodenoscopy (OGD). Before OGD the value for PVC was 30 +/- 2.5 pg/ml (means +/- SEM); during endoscopy it tended to increase slightly, to 35 +/- 3.2 pg/ml immediately after the examination (p greater than 0.05). By contrast with this finding, the SGC increased rapidly and significantly from 47 +/- 4.7 pg/ml prior to the examination to maximal values up to 68 +/- 6 pg/ml on inspection of the fundus (p less than 0,005), and was at a significantly increased level (p less than 0.05), with a value of 61.5 +/- 7.2 pg/ml, as much as thirty minutes after the examination. Sixty minutes after the examination the values had fallen to their original level (47.5 +/- 7.5 pg/ml). The present study shows that OGD has no significant influence on PVC, but that it is possible that stimulation of the VIP-ergic system is accompanied by a trivial increase in PVC. By contrast with this OGD significantly increases the concentration of endocrinally secreted gastrin, an effect which lasts as much as thirty minutes after the examination. The release of gastrin is a result of the combined effect of mechanical stimulation, distension due to insufflation of air and simultaneously induced neural influences. However, these mechanisms exert at most an insignificant influence on PVC - if indeed they have any effect on it at all.
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PMID:[Endoscopy of the upper gastrointestinal tract: changes in the concentration of vasoactive intestinal polypeptide and gastrin?]. 649 48

Peptide histidine isoleucine (PHI) is a newly discovered peptide from porcine intestine, which has sequence homologies with VIP, an established intestinal secretagogue. To study the effects of PHI in human jejunum, natural porcine PHI was infused intravenously at 10.7 +/- 1.7 pmol/kg/min (mean +/- SEM) in normal volunteers during steady state perfusion of the jejunum with an isotonic bicarbonate-electrolyte solution. Plasma PHI concentrations rose to 279 +/- 26 pmol/l (mean +/- SEM) in the first 20 minutes of the infusion reaching 417 +/- 45 at 40 minutes. At these concentrations PHI induced a net secretion of chloride and sodium and either decreased net absorption or increased net secretion of fluid and potassium, while bicarbonate transport remained unaffected. Peptide histidine isoleucine is a potent jejunal secretagogue in man.
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PMID:Peptide histidine isoleucine: a secretagogue in human jejunum. 654 31

Seven Sprague-Dawley rats (404-440 g) underwent a 90% jejuno-ileal bypass (JIB); the functional loop consisted of 1/3 ileum and 2/3 jejunum with the bypassed loop being anastomosed to the ascending colon. Seven control rats were sham-operated. After 35 days, the rats were fasted 18 hours and venous blood was collected. Immunoreactivity of gastrin, measured with an antibody binding equally to G17 and G34, was higher in the plasma of the JIB (256 +/- 55 SEM pg/ml) than control (85 +/- 9 pg/ml) rats. This agrees with recent human studies but is in conflict with results in less mature rats. VIP levels were not significantly different. Glucagon-like immunoreactivity measured with antibodies specific for the C- and N-terminal regions of the hormone, respectively, were also higher in the JIB (510 +/- 40 and 129 +/- 15 pg/ml) rats.
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PMID:Circulating immunoreactivities of gastrin, glucagon and VIP after jejuno-ileal bypass. 707 93

The possible involvement of nerves containing vasoactive intestinal polypeptide in Crohn's disease was investigated by immunocytochemistry and radioimmunoassay of specimens from 17 patients with well-defined clinical and histologic features of the disease. The characteristic pattern of slender fibers, evenly distributed across the gut wall, was seen in specimens taken from controls, which consisted of (a) specimens from uninvolved areas of gut from carcinoma resection (n = 17) and (b) jejunoileal specimens obtained during bypass operation for obesity (n = 8) as well as in four of the six specimens from patients with ulcerative colitis. In contrast, this characteristic pattern was lost in all 17 patients with Crohn's disease, the pattern being replaced by thickened and more intensely immunostained fibers. These changes were consistently found in the mucosa and submucosa, and in 13 of the Crohn's disease cases, the abnormal pattern was totally transmural, involving both the myenteric and submucous plexus as well as the muscle layers. There was a > 200% increase in VIP content, as determined by radioimmunoassay, in Crohn's disease (294 +/- 29 pmol/g wet wt, mean +/- SEM) in comparison with (a) ulcerative colitis (93 +/- 5 pmol/g [P < 0.001]), and (b) controls consisting of carcinoma resection (108 +/- 39) and bypassed gut from obese patients (86 +/- 27 [P < 0.001]). At least part of the previously documented autonomic nerve changes in Crohn's disease are, thus, due to an increase in vasoactive intestinal polypeptide innervation.
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PMID:Abnormalities of vasoactive intestinal polypeptide-containing nerves in Crohn's disease. 741 8

Radioligand assays of the membrane fraction of hen hypothalamic tissues involving the preoptic (HPOA) or median eminence (HMEA) areas revealed the presence of a specific binding component to chicken vasoactive intestinal peptide (cVIP) having properties of a receptor. The equilibrium dissociation constant (Kd) was 0.70 +/- 0.07 nM (Mean +/- SEM; N = 5) in HPOA and 1.02 +/- 0.15 nM (N = 5) in HMEA as estimated by Scatchard analysis of saturation studies, and was 0.91 +/- 0.11 nM (N = 3) (HPOA) and 1.25 +/- 0.09 nM (N = 3) (HMEA) as determined by a kinetic analysis. The maximum binding capacity (Bmax) obtained by Scatchard analysis was 167 +/- 19 fmol/mg protein (N = 5) (HPOA) and 133 +/- 17 fmol/mg protein (N = 5) (HMEA). The Kd and Bmax values obtained by Scatchard analysis were similar in the two areas of the hypothalamus and in both laying and nonlaying hens. Administration of cVIP in vivo caused a decrease in specific cVIP binding. These results suggest the presence of a VIP receptor in the hen hypothalamus.
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PMID:Presence of vasoactive intestinal peptide receptor in the hen hypothalamus. 762 62

In the present study, we examined the effect of pretreatment with VIP and various peptides structurally related to VIP such us PHI, helodermin, and secretin on VIP receptor number and affinity, as well as VIP-stimulated cyclic AMP production in rat peritoneal macrophages. Short-term (5-30 min) exposures of rat peritoneal macrophages to 0.1 microM VIP induced a rapid reduction in specific binding. Pretreatment for 15 and 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, causing a decrease of 67% (SEM = 6) in specific binding. Pretreatment with 0.1 microM VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respectively. Only VIP concentrations at the nanomolar level and higher were shown to be effective. The potency of VIP and related peptides to desensitize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was also studied. It was shown that receptor-bound ligand is internalized during the downregulation process. However, the diminution in VIP binding to macrophages was not completely explained by internalization.
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PMID:Homologous regulation of vasoactive intestinal peptide (VIP) receptors on rat peritoneal macrophages. 778 61

Our aim was to determine if extrinsic denervation alters the absorptive response of the colon to proabsorptive and prosecretory stimuli. Ten dogs underwent enteric isolation of a 50-cm proximal colonic segment; five were also randomized to undergo extrinsic denervation (DEN). At 2 and 13 wk postoperatively, net absorptive fluxes (mean +/- SEM) of water and electrolytes were determined during basal conditions and during proabsorptive low-dose (0.3 microg/kg/min) or high-dose (3 microg/kg/min) norepinephrine or prosecretory VIP (500 pg/kg/min). The net absorptive flux of water under basal conditions was decreased in DEN versus neurally intact controls at two weeks (4.0 +/- 0.6 vs 6.6 +/- 0.7 microl/min/cm, P = 0.03) but did not differ at 13 weeks (5.0 +/- 1.0 vs 5.7 +/- 0.9, P > 0.05). Low- and high-dose norepinephrine increased water absorption in both groups at two weeks; the change in flux for high-dose norepinephrine was greater in DEN versus controls (4.1 +/- 1 vs 2.1 +/- 0.6 microl/min/cm, P = 0.04). Net absorptive fluxes of Na+ and Cl- followed these trends. VIP did not alter absorption of water or electrolytes. Extrinsic denervation of the proximal colon causes a decrease in net colonic absorption and a transient, proabsorptive adrenergic hypersensitivity in colonic absorption of water and electrolytes. VIP does not have a net secretory effect in the proximal canine colon.
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PMID:Extrinsic denervation causes a transient proabsorptive adrenergic hypersensitivity in the canine proximal colon. 1218 26


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