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Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocin-diabetic rats.

Few previous studies have discussed the changes in serotonin receptor activity in the small intestine of diabetic animals. Therefore, we examined serotonin content in duodenal tissue and dose-dependent effects of serotonin agonists and antagonists on the motor activity of ex vivo vascularly perfused duodenum of streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased in enterochromaffin cells but not altered in serotonin-containing neurons in STZ-diabetic rats. Motor activity assessed by frequency, amplitude, and percent motility index per 10 min of pressure waves was reduced in the duodenum of diabetic rats, and this reduction was reversed by insulin treatment. Serotonin dose dependently increased the motor activity in control rat duodenum but only a higher concentration of serotonin increased the motor activity in diabetic rats. The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT(4)) antagonist SB-204070 dose dependently reduced motor activity in both control and diabetic rats, whereas the 5-HT(3) receptor antagonist azasetron, even at a higher concentration, failed to affect motor activity in diabetic rat duodenum but dose dependently reduced motor activity in control rat duodenum. These results suggest that 5-HT(3) receptor activity was impaired but 5-HT(4) receptor activity was intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT(3) receptor activity may induce the motility disturbance in the small intestine of diabetes mellitus.

Animals↗

Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.

Expressions of the cholecystokinin (CCK)-A and -B receptor genes in human duodenum, pancreas and gallbladder were examined by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. The autoradiographic study of CCK-A and -B receptors in the human duodenum and pancreas was examined in vitro. To determine the subtypes to CCK receptors in the pancreas or duodenum, we studied the abilities of CCK-A and -B receptor agonists (CCK-8 and gastrin) and antagonists (loxiglumide, L-364,718 and L-365,260) to inhibit binding of 125I-CCK-8. CCK-A receptor mRNA was not expressed in the human pancreas, but was expressed in the gallbladder and duodenum, although it was expressed in the pancreas by RT-PCR. CCK-B receptor mRNA was expressed in the pancreas, but not in gallbladder and duodenum. Using autoradiography, high concentrations of CCK-A receptors were detected in the duodenal mucosa, although in the pancreas only CCK-B receptors were detected by this method. These results suggest that localization of CCK-A receptor in human duodenum provides a biochemical and morphological basis for some physiological functions of CCK.

Autoradiography↗

Development and distribution of mast cells and neuropeptides in human fetus duodenum.

AIM: To study the developmental regularities and heterogeneity of mast cells (MC) in human fetus duodenum and the distribution and developmental regularities of substance P(SP), calcitonin gene-related peptide (CGRP)-immunoreactive (IR) peptidergic nerves in fetus duodenum, as well as the relationship between MC, SP and CGRP- IR peptidergic nerves. METHODS: Duodena from 21 cases of human fetus and one term infant were stained by hematoxylin-eosin (HE), toluidine blue (TB) and immunohistochemical avidin-biotinylated peroxidase complex (ABC) method. RESULTS: Lobe-shape intestinal villi in duodenum were already developed at the twelfth week. At the 21st wk, muscular mucosa appeared gradually, and four layers were observed in the wall of duodenum. TB staining showed that the granules in the immature MC were pale violet, while the mature MC were strong violet in color by TB staining. Connective tissue MC (CTMC) appeared occasionally in submucosa and muscular layer of duodenum at the 16th wk. While the mucosa MC (MMC) appeared at the 18th wk. At the 22nd wk, both CTMC and MMC were activated, and distributed in the surrounding blood vessels and ganglions. The verge of some MC were unclear, and showed degranular phenomena. At the 14th wk, SP and CGRP-IR nerve fibers and cells appeared in the myenteric and submucous plexuses in small intestine, and the responses were turn strongly. Neurons were light to deep brown, and nerve fibers were present as varicose and liner profiles. On the corresponding site of serial sections, SP and CGRP immunohistochemical reactions were coexisted in one nerve fiber or cell. Some of MC showed SP and CGRP-IR positive staining. CONCLUSION: There are two heterogeneous kinds of MC in duodenum, MMC and CTMC. MC might play an important role in regulating blood circulation and sensation.

Calcitonin Gene-Related Peptide↗

Effect of first part of duodenum on gastric emptying in dogs: response to acid, fat, glucose, and neural blockade.

Five dogs were prepared, each with a gastric and duodenal fistula (5 cm distal to the pylorus), to study the inhibitory role of the first 5 cm of the duodenum on gastric emptying. The basic design of the experiments was to instill the test meal (300 ml at 37 degrees C, containing phenol red 40 mg 1(-1)) into the stomach and collect it at 1- or 2-min intervals for 10 or 20 min from the duodenal fistula. As the test meal emptied from the stomach it bathed the first 5 cm of duodenum and thus stimulated the appropriate receptor. A Foley catheter with an inflated balloon prevented passage into the second part of the duodenum. Test meals of hypertonic glucose (15%, 865 milliosmoles kg-1) or 20 and 80 mM of sodium oleate emptied at the same rate as water when allowed to bathe the first 5 cm of duodenum, whereas test meals of 100 mM of HCl were slowed. In further studies using neural blocking agents, the emptying of water meals was slowed with subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous hexamethonium chloride (10 mg kg-1), and norepinephrine bitartrate (0.04 mg kg-1). The emptying of 100 to 120 mM HCl meals was slowed by subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous norepinephrine bitartrate (0.04 mg kg-1), and the intravenous alpha-receptor blocking agents phenoxybenzamine HCl (2 mg kg-1) and phentolamine (2 mg kg-1), was unaffected by intravenous hexamethonium chloide (10 mg kg-1), and was unchanged (1.0 mg kg-1) or slightly slowed (2.0 mg kg-1) by the beta-receptor blocker propranolol. In contrast, acid test meals were emptied at the same rate as water when treated with intravenous guanethidine monosulfate (2 mg kg-1) or intramuscular reserpine (1 mg kg-1), indicating that the acid inhibition was mediated by an adrenergic mechanism. The emptying of water meals was unchanged by these two drugs. The authors suggest that the first 5 cm of duodenum contain receptors for inhibition of emptying of acid but not for fat or hypertonic glucose. Furthermore, the neural blocking studies indicate that the inhibitory effect of acid in the first part of the duodenum is an adrenergic mechanism which appears to be neither alpha nor beta-receptor-mediated.

Animals↗

Multiple somatostatin- and gastrin-containing carcinoids of the duodenum: report of a case treated by pancreas-sparing duodenectomy.

A 59-year-old Japanese man was incidentally discovered to have multiple polyps in the duodenum by endoscopy during a health checkup. Laboratory studies showed an elevated level of serum somatostatin. The mutation of the MEN1 gene was not observed. An endoscopic examination revealed multiple polypoid lesions in the bulbus and in the second portion of the duodenum. An upper gastrointestinal series also showed the multiple polypoid lesions in the bulbus, and in the descending and horizontal portions of the duodenum. The biopsy specimen showed small monotonous cells with round nuclei compatible with a carcinoid tumor. The tumor cells were positive for somatostatin and gastrin. Based on the clinical diagnosis of multiple carcinoids of the duodenum, a pancreas-sparing duodenectomy was performed. Macroscopic findings showed about 30 polypoid lesions throughout the duodenum. The biggest one was not over 10 mm in size. A histological examination revealed well-demarcated carcinoid tumors located in the submucosal layer. Immunohistochemically, the tumors were diffusely positive for somatostatin and were scatteringly positive for gastrin. The patient's postoperative course of treatment was uneventful and his postoperative serum somatostatin went down to normal range. The pancreas-sparing duodenectomy is a safe and effective treatment in patients with multiple carcinoids of the duodenum, that are smaller than 1 cm in size.

Ampulla of Vater↗

[The reinsertion of the duodenum into the digestive circuit. The indications and surgical technics in operated stomach syndromes].

The authors analyse, retrospectively, the experience of the Clinic of Surgery III. Cluj-Napoca, in the indications and surgical methods for reintroducing the duodenum in the digestive circuit in the syndromes of the stomach operated for benign affections. Between 1974 and 1987, the duodenum was reinstated in the digestive circuit in 37 patients, operated previously for duodenal ulcer (32 cases), gastric ulcer (3 cases), syndrome of mesenteric clip (2 cases). The primary surgeries that led to the exclusions of the duodenum from the digestive tract were gastroenteroanastomosis in 4 cases, and the gastric resections with gastrojejunal anastomoses of the Billroth II type in 33 cases (Reichel-Polya in 28 cases. Hoffmeister-Finsterer in 3 cases, Roux in 2 cases). The reintroduction of the duodenum in the digestive circuit, based on clinical and paraclinical criteria, was indicated in anastomotic ulcer (in 17 cases), gastric ulcer following gastroenteroanastomoses (in 1 case), syndrome of afferent loop (in 11 cases), persistent "dumping" syndrome (in 8 cases), association of plurideficiency syndrome (in 54% of the cases). The way of reconstructing the duodenum was adapted to the type and correctness of the primary operation, to the dominant clinical syndrome and associated lesions to the biological background and possibilities offered by the intrasurgical situation: reconversion by direct gastroduodenal anastomosis after degastrogastrectomy was used in 31 cases, the indirect methods by transposition of the afferent loop (Soupault--Bucaille) in 4 cases, or of the afferent one (Henley)--1 case gastrography and segmentary enterectomy in 1 case. The postoperative complications appeared in 35.1% of case, with a mortality of 8.1%. The therapeutic results were good and very good in 89.3% of the cases. The authors insist on the importance of maintaining the duodenum in the digestive circuit, during the primary surgeries for preventing some severe postsurgical syndromes.

Anastomosis, Surgical↗

The effect of chronic acidification of the canine duodenum on gastrin release from the antrum transplanted into the colon.

Exogenous infusion of acid into the canine duodenum inhibits acid secretion stimulated by endogenously released and exogenously administered gastrin. The importance of this mechanism in normal acid homeostasis and in the inhibition of chronic endogenous acid hypersecretion is not established. In this study the classic Dragstedt model antral colonic transplant (ACT) was used to produce endogenous hypergastrinemia and acid hypersecretion. The effects of the ACT when the duodenum was retained in continuity with the stomach (gastroduodenostomy) were compared with those obtained when the duodenum was no longer in continuity with the stomach (gastrojejunostomy). The duodenum markedly suppressed gastrin release (p = 0.003) and gastric acid secretion (p = 0.005) in each of the four dogs. The dogs remained free of ulcers for 8 months after gastroduodenostomy and ACT. However, after conversion to gastrojejunostomy, large, chronic peptic ulcers developed after a mean of 3.5 months. The inhibitory effect of the duodenum on gastric release and gastric acid secretion protected the dog against ulceration for an extended period. The duodenum may be the major site of inhibitory control of acid secretion and endogenous gastrin release in dogs.

Anastomosis, Surgical↗

Intramural distribution of regulatory peptides in the human stomach and duodenum.

The distribution of regulatory peptides was studied by radioimmunoassay in the separated mucosa, submucosa and muscularis externa of the human oxyntic stomach, antrum and duodenum. Immunoreactive gastrin, secretin, gastric inhibitory polypeptide and motilin were virtually confined to the mucosa and duodenal submucosa, where endocrine cells are present. Only minor amounts of motilin and gastrin (3.2 +/- 0.5% and 4.3 +/- 0.8% of their total content, means + SEM, respectively) were found in the separated duodenal muscle. Somatostatin-, vasoactive intestinal polypeptide-, substance P-, and mammalian bombesin-like peptides showed distinct differential distributions in all layers. Substance P was low in the stomach and markedly increased in the duodenum, especially in the mucosa (fundus 0.8 +/- 0.2 pmol/g, duodenum 66 +/- 12). Vasoactive intestinal polypeptide and somatostatin, although well represented in the stomach, also increased in the duodenum in all layers of the wall (whole fundus 281 +/- 33 and 334 +/- 46 pmol/g, antrum 124 +/- 18 and 426 +/- 59, duodenum 507 +/- 99 and 1816 +/- 149, respectively). Mammalian bombesin immunoreactivity was comparatively abundant in the oxyntic stomach (mucosa 34 +/- 4.5 pmol/g, muscularis externa 29 +/- 4.8), less so in the antrum (6.3 +/- 1.5 and 11 +/- 3.2 pmol/g, respectively). Low concentrations of this peptide were measured in the duodenum, practically confined to the muscle (this layer 5.1 +/- 1.5 pmol/g, or 83 +/- 5.6% of the total content).

Aged↗

Immunohistochemical studies on the ontogenesis of some endocrine cells in the chicken antrum and duodenum.

The time of appearance, morphology and topographic distribution of gastrin/CCK-, somatostatin-, 5HT-, and bombesin-like immunoreactive cells during embryonic and postnatal development were studied in chicken antrum and duodenum with immunohistochemical methods. Gastrin/CCK-like cells appeared on or about the 11th day in the antrum and duodenum, somatostatin-like cells around the 12th day in the antrum and the 11th day in the duodenum, bombesin-like cells appeared only in the antrum and only at hatching. In the early stages of development all the immunoreactive cells were localized in the surface epithelium, descending deeper into the glands as these form, although some cells could always be seen in the surface epithelium. Around the 17th day the number of gastrin/CCK-like cells and somatostatin-like cells in the antrum increases, while 5HT-like already become more numerous in the duodenum from the 13th day onwards. Two territories were recognized in the antrum of the adult: the first was near the duodenum where gastrin/CCK-like and somatostatin-like cells, often in close contact, were very numerous; the other territory was near the gizzard where bombesin-like cells were more numerous. Both regions contained 5HT-like cells in smaller number. In adult duodenum, 5HT-like cells were the most numerous, while somatostatin-like cells and gastrin/CCK-like cells, found in more superficial locations, were more scanty.

Animals↗

Clinical and pathologic features of the nodular duodenum.

Nodular duodenum, frequently described as nodular duodenitis, is endoscopically characterized by multiple erythematous nodules in the proximal duodenum and may represent a variant of duodenal inflammation. This study examines the incidence, clinical presentation, histologic correlates, natural history, and response to therapy of nodular duodenum in 83 patients who presented with epigastric pain, heartburn, early satiety, bloating, nausea, vomiting, or gastrointestinal bleeding. There was a previous history of peptic ulcer disease in 58% of patients and gastroesophageal reflux in 33%. None of the patients had associated end-stage renal disease. Endoscopically, in addition to nodular duodenum, esophagitis was found in 17% of patients and gastritis in 32%. Histology of duodenal nodules revealed chronic inflammation in 58% of patients, Brunner's gland hyperplasia in 9%, gastric heterotopia in 7%, and normal mucosa in 26% of patients. In a group of 34 patients studied prospectively, high dosage (300 mg orally bid) therapy with the H2-antagonist ranitidine for 8 wk significantly improved symptoms and endoscopic appearance (p < 0.05). In 26 patients who completely or partially failed H2-antagonist therapy, continuation of therapy with omeprazole (40 mg orally qd) for 8 wk significantly improved symptoms and endoscopic findings (p < 0.05) in 10 patients. These therapeutic approaches led to improvement in the endoscopic findings, but to no statistically significant changes in the underlying histologic appearance of the duodenum. We conclude that nodular duodenum is an endoscopically distinct entity that may respond clinically to antisecretory therapy, but remains difficult to eradicate completely.

Adult↗

[Treatment of injuries of the duodenum and pancreas].

The authors study 84 patients that had damages of the duodenum and or pancreas and underwent different types of surgery. In 39 patients who had damage only in the duodenum; there were 2 (4.0%) duodenal fistulas, and 3 (6.0%) intraperitoneal abscess. In 38 patients who had injuries only in the pancreas; there were 6 (13.1%) acute pancreatities, pancreatic fistulas and 1 (2.2%) pancreatic pseudocyst. In 7 cases, injuries were found to both pancreas and duodenum. The author reports 1 case of duodenal fistula (14.3%) 1 case of acute pancreatitis (14.3%) and 3 cases of pancreatic fistula (43.0%). Only 7 patients died (8.3%), and of these 2 died for reasons not directly related to the operatory technic used. A simple suture can be performed in those cases where a complete section of the duodenum is unnecessary and there is no injury to the duodenal papilla. A burying suture of the stomas associated with a side-to-side duodenojejunal anastomosis should be preferred in the complete section of the duodenum localized beyond the ampulla of Vater. In all superficial wounds of small extension a suture of the pancreas should be performed. Distal pancreatectomy of body or tail should be made in the wounds with a possible lesion to the Wirsung duct and when there is an extensive glandular lesion. The associate wounds of duodenum and pancreas should be treated as if they were isolated lesions.

Abdominal Injuries↗

Pancreatic head resection with and without preservation of the duodenum: different postoperative gastric motility.

BACKGROUND: Early gastric stasis is a unique complication of pylorus-preserving pancreatoduodenectomy. Because the duodenum proved to be important in the initiation and consolidation of phase III activity of the migrating motor complex of the stomach, the absence of the duodenum and hence gastric phase III may be a cause of gastric stasis. METHODS: Postoperative gastrointestinal motility was measured with a pneumohydraulic capillary infusion system in nine patients who had undergone pylorus-preserving pancreatoduodenectomy through an indwelling tube assembly placed at operation, and compared with that in six patients who had undergone duodenum-preserving pancreatic head resection. Plasma motilin concentrations were measured by radioimmunoassay. RESULTS: The mean period until the first occurrence of gastric phase III was significantly longer in patients who had undergone a pylorus-preserving pancreatoduodenectomy (40.6 +/- 4.6 days or more) than in patients who had undergone a duodenum-preserving pancreatic head resection (18.8 +/- 4.3 days; p < 0.05). On the day of the first observation of gastric phase III, the plasma concentration of motilin at proximal jejunal phase III in patients who underwent a pylorus-preserving pancreatoduodenectomy (50.2 +/- 9.8 pg/ml) was significantly lower than that at duodenal phase III in patients who underwent a duodenum-preserving pancreatic head resection (184.6 +/- 48.6 pg/ml; p < 0.05). CONCLUSIONS: Gastric stasis after a pylorus-preserving pancreatoduodenectomy may be in part attributable to the low concentration of plasma motilin caused by the resection of the duodenum.

Aged↗

1,25(OH)(2)-vitamin D(3) affects the subcellular distribution of protein kinase C isoenzymes in rat duodenum: influence of aging.

We have previously shown that the steroid hormone 1, 25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] stimulates total cell protein kinase C (PKC) activity in rat duodenum, an effect that is severely impaired in old animals. We further examined the role of 1, 25(OH)(2)D(3) on PKC as it relates to aging by measuring hormone-induced changes in subcellular localization of PKC activity and isoenzymes in duodenal mucosae from young (three-month-old) and aged (24-month-old) rats. Short treatment of duodenum with 1, 25(OH)(2)D(3) (0.1 nM, 1 min) increased membrane-associated PKC activity, whereas it decreased the activity in the cytosol of young rats but was without significant effect in aged animals. Furthermore, the ability to translocate was present in young animals after a short treatment with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA; 100 nM) or dioctanoyl-glycerol (50 microM), whereas the ability was absent in aged rats, suggesting that PKC function was impaired with aging independent of agonist stimulation. The expression of specific PKC isoenzymes and changes in their subcellular distribution after short exposure of the duodenum to the hormone were determined. Western blot analysis of total homogenates using antibodies to various PKC isoforms allowed detection of PKC alpha, beta, and delta. The expression of the straight theta and the zeta isoforms was in addition demonstrated by reverse transcription-polymerase chain reaction. The pattern of isoenzymes present in the duodenum was unaffected by aging. In young rats, 1, 25(OH)(2)D(3) translocates PKC alpha, beta, and delta to the membrane and nucleus; however, no translocation of PKC isoforms was observed in 24-month-old animals in response to the hormone. In summary, in rat duodenum, 1,25(OH)(2)D(3) modulation of PKC activity and isoenzyme subcellular distribution are impaired with aging and may explain age-induced alterations in the intestinal processes under the control of the hormone.

Aging↗

Configuration of the straight veins and their intramural anastomoses in the human duodenum: an anatomical study using cast specimens.

BACKGROUND/PURPOSE: There have, hitherto, been no anatomical investigations of the intramural venous system of the duodenum. METHODS: Intramural longitudinal anastomoses of the straight veins in the human duodenum were investigated, using 15 latex resin cast specimens. RESULTS: The venous tree (with a straight vein as the trunk) was developed well, with numerous twigs (venules). We identified two types of longitudinal anastomoses between the straight veins; the direct and plexus-mediated types, with an equal incidence. The direct-type anastomosis was 0.1-0.5 mm in minimum diameter along the course and communicated in almost a straight line between the mother straight veins. In contrast, the plexus-mediated type was regarded as the thickest route (almost 0.1 mm) in the suggested submucosal venular network in the duodenal wall. These two types of anastomoses were distributed almost equally in most of the duodenum, although a relatively lower density was found in the superior portion. On the ventral side of the duodenum, the thicker straight veins had anastomotic branches significantly more frequently than the thinner ones (P = 0.0018). CONCLUSIONS; These results seemed to support the feasibility of Kocher mobilization, as well as the conventional poor preservation of the duodenal venous system during duodenum-preserving surgery. However, because the intramural longitudinal venous anastomoses were limited in number and location, we recommend preservation of the posterior superior pancreaticoduodenal vein and either of the inferior venous arcades, in combination with their concomitant arteries, in exchange for the unavoidable sacrifice of Henle's trunk and the dorsal pancreatic vein.

Aged↗

Duodenum preservation in pancreatic head resection to maintain pancreatic exocrine function (determined by pancreatic function diagnostant test and cholecystokinin secretion).

BACKGROUND/PURPOSE: Organ-preserving surgery, such as pylorus-preserving pancreatoduodenectomy (PPPD), duodenum-preserving pancreatic head resection (DPPHR), or medial pancreatectomy (MP), is one of the recent advances in pancreatic surgery. There was a previous report that preservation of the duodenum maintained pancreatic function. However, concerning the resected pancreas, patients were divided into two groups; one group included pancreatic head resections such as Whipple, PPPD, and complete DPPHR, and the other group included MP that removed only the pancreatic neck and preserved the pancreatic head and distal pancreas. The present study was designed to clarify the significance of duodenum preservation, in comparison with duodenum removal, in patients with pancreatic head resection, in terms of pancreatic function, determined by a pancreatic function diagnostant (PFD) test and cholecystokinin (CCK) secretion. METHODS: The subjects were 61 patients (10 with Whipple, 41 with PPPD, and 10 with complete DPPHR). PFD tests and postprandial plasma CCK secretion were used for evaluation. RESULTS: There was a significant difference between pre- and postoperative PFD values in the patients who received Whipple or PPPD; however, there was no difference in those who had complete DPPHR. Concerning the postoperative PFD value, complete DPPHR was superior to Whipple and PPPD. Regarding postprandial CCK secretion, the pre- and postoperative values were significantly different in the patients with Whipple or PPPD, but there was no difference in those with complete DPPHR. Comparing the three kinds of operations, complete DPPHR was superior to the other two procedures in its maintenance of pancreatic function. There was the significant correlation between CCK and PFD in our patients in the Spearman Rank Correlation (P < 0.0029) and Fisher's r to z (P < 0.0058). CONCLUSIONS: When pre- and postoperative pancreatic exocrine function and postprandial CCK secretion were measured in patients with pancreatic head resection, it was found that preservation of the entire duodenum was an important factor for maintaining pancreatic function.

Cholecystokinin↗

Healing of incisional wounds in stomach and duodenum. A biomechanical study.

The healing pattern of incisional wounds in the rat stomach and duodenum was determined. A model allowing the biomechanical determinations of complete load-deformation curves is described. Wounds were made in the nonglandular (rumen) and glandular oxyntic (corpus) parts of the stomach and in duodenum. The wounds were tested 5 to 40 days after operation. Of the intact tissues the nonglandular part of the stomach was found to be more extensible and required more energy to be ruptured than the glandular part of the stomach and duodenum. The healing wounds in the glandular part of the stomach and duodenum showed the most rapid increase in mechanical strength, and after 40 days both required more energy to be ruptured than intact tissue. Wounds in the nonglandular part of the stomach reached only 75% of intact strength value after 40 days. The process of wound healing resulted in an increase in tissue stiffness. These findings indicate that wound healing in stomach and duodenum is more rapid than that in most other tissues and that the load-strain data give a detailed picture of the healing process. The energy required to rupture a wound represents the most informative assessment of wound healing.

Animals↗

[125I]S(-)-zacopride labels a novel 5-hydroxytryptamine sensitive recognition site in rat duodenum and ileum.

Autoradiographic binding studies using [125I]S(-)-zacopride (0.1 nM) identified non-5-HT3 specific binding sites (defined by 5-hydroxytryptamine (5-HT), 1.0 microM) in the rat duodenum and ileum and some other peripheral tissues (adrenal gland, liver, stomach, kidney and spleen). In the rat duodenum and ileum, saturation studies with [125I]S(-)-zacopride indicated that the specific binding was saturable and of high affinity to an apparently homogenous population of binding sites (duodenum Bmax = 1.88 fmol/mg, Kd = 0.078 nM; ileum Bmax = 1.60 fmol/mg, Kd = 0.071 nM). Competition studies with slices of either duodenum or ileum indicated that the pharmacology of the [125I]S(-)-zacopride recognition site in both tissues was comparable but differed from all 5-HT receptors and uptake sites reported to date. However, the [125I]S(-)-zacopride recognition site displayed some pharmacological and regional similarity to the 5-HT1P recognition site: The sensitivity of the [125I]S(-)-zacopride binding in the duodenum and ileum to GTP indicates that the radiolabelled recognition site may represent a functional G-protein coupled receptor.

Animals↗

The in vitro release of immunoreactive dynorphin and alpha-neoendorphin from the perfused rat duodenum.

The release of immunoreactive (ir) dynorphin (DYN) and alpha-neoendorphin (ir-ANEO) from the isolated perfused rat duodenum was demonstrated using specific radioimmunoassays (RIAs). Depolarization of the tissue by increasing the potassium (K+) concentration up to 108 mM enhanced the release of ir-DYN and ir-ANEO in Ca2+-dependent manner. Administration of the serotonin-releasing agent fenfluramine (10(-6) M) and the serotonin receptor agonist m-chlorophenylpiperazine (m-CPP, 10(-6) M) stimulated the release of ir-DYN and ir-ANEO from the duodenum. A subsequent study revealed that serotonin (5-HT, 10(-6)-10(-4) M) induced a dose-dependent increase in the release of ir-DYN and ir-ANEO from the duodenum. The effect of 5-HT on the release of ir-DYN and ir-ANEO from the duodenum was antagonized by 5-HT antagonist cyproheptadine (10(-6) M). The presence of dynorphin and the related peptides in the gastrointestinal tract (GIT) and their release from the duodenum in vitro indicate that these peptides may act as transmitters involved in some GIT functions. Furthermore, our results suggest that at least part of 5-HT effects on the GIT may be mediated by the release of dynorphin and the related peptides.

Animals↗