Endogenous prostaglandin I2 regulates the neural emergency system through release of calcitonin gene related peptide

BACKGROUND: We previously reported that endogenous prostaglandin I(2), generated by a mild irritant, sensitised calcitonin gene related peptide (CGRP) containing sensory nerves and facilitated the release of CGRP and gastric mucosal protection against ethanol. Administration of capsaicin also inhibited ethanol induced gastric mucosal injury through immediate release of CGRP from primary sensory neurones, which is termed the neural emergency system. In the present study, we tested whether endogenous prostaglandin I(2) also modulates the cytoprotective action of capsaicin using prostaglandin I receptor knockout mice (IP(-/-)). METHODS: The stomachs of IP(-/-) or their wild-type counterparts (IP(+/+)), anaesthetised with urethane (1.225 g/kg), were doubly cannulated from the oesophageal and duodenal sides, and the gastric mucosa was perfused (1 ml/min) with physiological saline. Perfusate was changed to 50% ethanol alone, or 50% ethanol containing capsaicin (16 approximately 1600 micro M). The injured area was estimated at the end of each perfusion experiment. In some animals, CGRP-(8-37), a CGRP antagonist (0.3 mg/kg), or indomethacin (1 mg/kg) was intravenously injected before perfusion of 50% ethanol containing capsaicin. RESULTS: Capsaicin inhibited the injured area in a dose dependent manner. Fifty per cent ethanol containing capsaicin (480 micro M) immediately increased intragastric levels of CGRP although 50% ethanol alone did not. The protective action of capsaicin (480 micro M) against ethanol was completely abolished by intravenous injection of CGRP-(8-37). Indomethacin also inhibited the protective action of capsaicin, and this was accompanied by reduced levels of intragastric CGRP. Intragastric levels of prostaglandin E(2) were not increased by capsaicin treatment but those of 6-keto-prostaglandin F(1alpha), a metabolite of prostaglandin I(2), were markedly increased. No protective action of capsaicin was observed in IP(-/-) which lacked the ability to increase intragastric CGRP levels in response to ethanol containing capsaicin. The CGRP content of the stomach from untreated IP(-/-) did not differ from those in IP(+/+). Capsaicin (160 micro M) together with intragastric perfusion of beraprost sodium (PGI(2) analogue, 2.5 micro g/ml) showed enhanced protection against ethanol induced injury. This enhanced protection was completely blocked by intravenous injection of CGRP-(8-37). CONCLUSIONS: The present results suggest that endogenous prostaglandin I(2) enhances the protective action of the capsaicin mediated neural emergency system against ethanol induced gastric mucosal injury through enhancement of CGRP release.     

Involvement of Capsaicin-Sensitive Sensory Neurons in Stress-Induced Gastroduodenal Mucosal Injury in Rats

The pathogenesis of stress-induced gastroduodenal mucosal injury is complex and incompletely understood. The aim of this investigation was to examine the involvement of gastric and duodenal capsaicin-sensitive neurons in mucosal damage associated with water-restraint stress (WRS) in rats. Following WRS, gastroduodenal mucosal injury was quantitated by macroscopic and microscopic methods. Calcitonin gene-related peptide (CGRP) content was measured by radioimmunoassay. WRS-induced mucosal erosive injury in the stomach and duodenum (40.9 ± 4.2 and 5.1 ± 0.6 mm², respectively) was reduced significantly (by 88% and 67%, respectively) by acute intragastric capsaicin administration prior to WRS. In contrast, sensory denervation by chronic capsaicin significantly increased the area of gastric injury and duodenal damage. WRS alone caused a significant reduction (by 52% and –35%, respectively) in gastric and duodenal CGRP content, which was prevented by acute capsaicin treatment. The data suggest that gastric and duodenal sensory neurons and CGRP are involved in the pathogenesis of stress-induced mucosal injury to the stomach and duodenum.     

Suppression of myoelectrical activity of gastric smooth muscle by endogenous gastric prostaglandin E2

The myoelectrical activity of the gastric smooth muscle, recorded by a bipolar electrode placed at the gastric antrum in rats, could be recorded when the stomach was distended with 5 ml of physiological saline. This activity may be induced by a mucosal reflex and was inhibited both by atropine and by pirenzepine. Replacement of physiological saline with solutions of NaCl suppressed this myoelectrical activity. This suppression was dependent on the concentrations of NaCl in the solutions, from 0.3 to 1.0 M. Pretreatment with indomethacin (10 mg/kg, intravenous) completely prevented this suppression induced by different concentrations of NaCl solutions. Intragastric administration of 1.0 M NaCl in solution caused an increase in the levels of PGE2 in the gastric lumen. Intragastric administration of OU-1308, a synthetic derivative of PGE1, also suppressed the myoelectrical activity in a dose-dependent manner. It is concluded that the suppression of gastric myoelectrical activity by hyperosmolar NaCl may be attributable to the generation of endogenous PGE2 in the stomach.     

Effects of posture on the physiology of gastric emptying: a magnetic resonance imaging study

OBJECTIVE: Gastric contents empty from the stomach despite frequent changes in body position. The mechanism that maintains gastric emptying independent of position is poorly understood. The aim of this study was to determine the effects of body position on gastric emptying and motor function. MATERIAL AND METHODS: Twelve volunteers were investigated in seated position (SP) and upside-down position (UDP) after ingestion of 300 ml water. Magnetic resonance imaging provided a non-invasive assessment of gastric emptying and volumes, intragastric distribution and peristaltic function. RESULTS: A marked difference in distal/proximal intragastric distribution between UDP and SP was present (7% versus 40%; p < 0.01). Gastric-emptying time was similar but emptying pattern was linear in UDP and exponential in SP. Peristalsis was slower in UDP than SP (2.75 versus 2.96 min-1; p < 0.01), but no correlation was found between peristaltic frequency and the rate of gastric emptying in either position. Postprandial volume response (gastric relaxation) was greater in UDP than SP (280 versus 250 ml; p < 0.05). A correlation was found between gastric relaxation and gastric-emptying time in SP (r2=0.46) but not in UDP. CONCLUSIONS: The stomach maintains the rate of gastric emptying despite radical changes in body position and intragastric distribution of gastric contents. In SP, hydrostatic pressure (modulated by gastric tone) dictates the gastric emptying. In UDP, gastric emptying also appears to be mediated by continuous adaptation of gastric tone. These findings provide support for the hypothesis that the mechanism of gastric emptying resembles a "pressure pump" rather than a "peristaltic pump".     

Differential effect on neuropeptide release of different concentrations of hydrogen ions on afferent and intrinsic neurons of the rat stomach.

In the muscle layer of the glandular portion of the rat stomach, in vivo capsaicin pretreatment markedly reduced calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but did not affect substance P-like immunoreactivity (SP-LI). Accordingly, in vitro superfusion of slices of this tissue with capsaicin (10 mumol/L) released CGRP-LI but not SP-LI, whereas both neuropeptides were released by 80 mmol/L K+. Exposure to relatively low-pH (pH 6) physiological salt solution induced an increase in the CGRP-LI outflow that was reduced by 70% in a Ca(2+)-free medium and was completely abolished by a previous exposure to capsaicin. However, superfusion with pH-6 medium did not produce any detectable SP-LI release. After exposure to pH-6 medium, both capsaicin and high-K+ medium were still able to release a consistent quantity of CGRP-LI and SP-LI, respectively. Increased mucosal blood flow induced by acid back-diffusion is considered a protective mechanism against mucosal gastric lesion. The present findings suggest that hydrogen ions diffusing into the gastric wall may promote protective vasodilatation by activating the "efferent" function of capsaicin-sensitive nerves without affecting the secretory process of other intrinsic peptidergic neurons.     

Gastric electrical stimulation in patients with gastroparesis

Abstract As in the heart, there is a pacemaker in the human stomach and it generates myoelectrical activity with a frequency of approximately three cycles per minute. Abnormalities in gastric myoelectrical activity may result in gastric motility disorders, such as gastroparesis. Electrical stimulation of the stomach is achieved by delivering electrical currents via electrodes attached to the smooth muscle of the stomach. Recently, a number of studies on electrical stimulation of the stomach in both humans and dogs have indicated that gastric electrical stimulation with appropriate parameters is able to entrain gastric slow waves and normalize gastric dysrhythmias. This has led some investigators to use gastric electrical stimulation to treat patients with gastroparesis. Previous studies and the current state of the field in gastric electrical stimulation in treatment of gastroparesis will be discussed and summarized.     

Vasodilatation by calcitonin gene-related peptide and by substance P: a comparison of their effects on resistance and capacitance vessels of human forearms

A comparison has been made of the effects of the potent vasodilating peptide calcitonin gene-related peptide (CGRP) and substance P (SP) on resistance and capacitance vessels of normal subjects. Brachial artery infusion of 1.25 to 10 pmol/min CGRP and of 0.25 to 1.5 pmol/min SP produced maximal increases in forearm blood flow (177 +/- 75% and 198 +/- 50%, respectively), as measured by venous occlusion plethysmography. The vasodilation due to CGRP was prolonged, with a half-life of biological effect of approximately 18 min, while that due to SP was of short duration, with a half-life of biological effect of approximately 15 sec. There was rapid development of tachyphylaxis to the effects of arterial infusion of SP, but not of CGRP, during a prolonged infusion at one dose. CGRP did not alter the diameter of a superficial hand vein, either at rest or when the vein was constricted by a simultaneous infusion of norepinephrine or by the single deep breath reflex. In contrast, SP caused dilatation of veins preconstricted with norepinephrine, although the effect was only transient and dose-response curves could not be constructed. The venoconstrictor response to a single deep breath was abolished by SP. Simultaneous arterial infusion of both peptides produced at least additive, and possibly synergistic, effects on forearm blood flow. We propose that both CGRP and SP have a role in the regulation of vascular smooth muscle tone.     

Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS: We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. RESULTS: Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 μg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION: GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.     

Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats

BACKGROUND: Effects of vanilloid-receptor agonists and antagonists on HCl-induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms. METHODS: Gastric lesions in rats were evaluated after intragastric administration of 0.6 N HCl. The localization of VR1 in the stomach was investigated immunohistochemically. RESULTS: Intragastric administration of capsaicin inhibited the formation of gastric lesions in a dose-dependent manner (0.1-2.5 mg/kg). The functional VR1 antagonists ruthenium red and capsazepine markedly aggravated HCl-induced gastric lesions in rats. The gastroprotective effect of capsaicin was attenuated by ruthenium red or capsazepine. It is reported that resiniferatoxin, [6]-gingerol and lafutidine are compounds that activate VR1 and/or capsaicin-sensitive afferent neurons. These compounds significantly inhibited the formation of HCl-induced gastric lesions, and their gastroprotective effects were inhibited by treatment with ruthenium red. The immunohistochemical studies revealed that nerve fibers expressing VR1 exist along gastric glands in the mucosa, around blood vessels in the submucosa, in the myenteric plexus, and in the smooth muscle layers, especially the circular muscle layer. CONCLUSION: The results of this study suggest that VR1 plays a protective role in the gastric defensive mechanism in rats.     

Gastric inflammation triggers hypersensitivity to acid in awake rats

BACKGROUND & AIMS: Changes in visceral sensation contribute to the development of dyspepsia. Nonhuman models have previously focused on responses to mechanical stimulation. We studied the response to acid stimulation in the normal and inflamed stomach in rats. METHODS: A balloon and gastrostomy catheter were implanted into the stomach. Electromyographic responses to gastric balloon distention or acid administration through the gastrostomy were recorded from the acromiotrapezius muscle. To characterize chemonociceptive pathways, 0.75 mL HCl (0.05-0.3 N) or saline were given intragastrically in controls and animals after vagotomy, splanchnic nerve resection, or chemical denervation with capsaicin. The effect of inflammation was examined after induction of mild diffuse gastritis using iodoacetamide or creating gastric ulcers by injecting 60% acetic acid for 45 seconds into a clamped area of the stomach. RESULTS: Visceromotor electromyographic responses increased within 2 minutes after HCl administration (0.15 and 0.3 mol/L) but not saline or lower acid concentrations. Vagotomy and pretreatment with capsaicin but not splanchnic nerve resection abolished this response. Prior acid administration did not acutely sensitize animals to subsequent gastric distention. Gastritis and gastric ulcers enhanced the visceromotor responses to intragastric acid. CONCLUSIONS: In awake rats, visceromotor responses to intragastric acid are quantifiable, reliable, and reproducible. Aversive responses to acute noxious chemical stimuli primarily require vagal but not spinal sensory pathways. Injury-induced sensitization to intragastric acid administration is consistent with a potential role of chemical stimulation in triggering dyspeptic symptoms.     

Protective role of vanilloid receptor type 1 in HCl‐induced gastric mucosal lesions in rats

Background: Effects of vanilloid‐receptor agonists and antagonists on HCl‐induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms. Methods: Gastric lesions in rats were evaluated after intragastric administration of 0.6?N HCl. The localization of VR1 in the stomach was investigated immunohistochemically. Results: Intragastric administration of capsaicin inhibited the formation of gastric lesions in a dose‐dependent manner (0.1–2.5?mg/kg). The functional VR1 antagonists ruthenium red and capsazepine markedly aggravated HCl‐induced gastric lesions in rats. The gastroprotective effect of capsaicin was attenuated by ruthenium red or capsazepine. It is reported that resiniferatoxin, [6]‐gingerol and lafutidine are compounds that activate VR1 and/or capsaicin‐sensitive afferent neurons. These compounds significantly inhibited the formation of HCl‐induced gastric lesions, and their gastroprotective effects were inhibited by treatment with ruthenium red. The immunohistochemical studies revealed that nerve fibers expressing VR1 exist along gastric glands in the mucosa, around blood vessels in the submucosa, in the myenteric plexus, and in the smooth muscle layers, especially the circular muscle layer. Conclusion: The results of this study suggest that VR1 plays a protective role in the gastric defensive mechanism in rats.     

Abnormal gastric myoelectrical activity and delayed gastric emptying in patients with symptoms suggestive of gastroparesis

Gastric myoelectrical activity modulates gastric motor activity. Abnormalities in gastric myoelectrical activity may be associated with gastric motility disorders. The aim of this study was to investigate the correlation of gastric myoelectrical activity with gastric emptying in symptomatic patients with and without gastroparesis. Ninety-seven patients with symptoms suggestive of gastroparesis participated in the study. Gastric myoelectrical activity was recorded using surface electrogastrography. The electrogastrogram (EGG) was recorded for 30 min in the fasting state and for 120 min after a solid test meal. Gastric emptying of the solid meal was simultaneously monitored for 120 min. Patients with delayed gastric emptying showed a significantly lower percentage of normal gastric slow waves (P<0.03) and a significantly reduced increase of the dominant power in the postprandial EGG (P<0.02). Postprandial EGG parameters were found to be able to predict delayed emptying of the stomach. Postprandial gastric dysrhythmia predicts delayed gastric emptying with an accuracy of 78%, while the abnormality in postprandial EGG power predicts delayed gastric emptying with an accuracy of 75%. All patients with abnormalities in both the rhythmicity and the power had delayed gastric emptying. Patients with delayed gastric emptying have a lower percentage of normal gastric slow waves in the EGG and a lower postprandial increase in the dominant power. Abnormalities in the postprandial EGG seem to be able to predict delayed emptying of the stomach. However, a normal EGG does not seem to guarantee normal emptying of the stomach.     

Effect of sildenafil on gastric emptying in healthy adults

Background and Aim: Phosphodiesterase type 5 hydrolyzes and inactivates cyclic guanosine monophosphate produced by the nitric oxide‐stimulated guanylate cyclase. Sildenafil is a potent, reversible, and highly selective inhibitor of this phosphodiesterase. It causes smooth muscle relaxation by increasing intracellular concentrations of cyclic guanosine monophosphate. The aim of this study was to test the hypothesis that sildenafil alters gastric emptying and the intragastric distribution of food in healthy adults. Methods: Nine normal subjects (mean age 28 years, range 25–33) were given a placebo or a tablet of sildenafil (50 mg) at different times along with radio‐opaque markers. A gastric emptying scan was used to calculate the t_1/2 for gastric emptying (the time taken for the initial radioactivity to fall by 50%). Intragastric food distribution was also assessed using the gastric emptying scan to calculate proximal gastric emptying t_1/2, the proximal volume (the highest activity value in the proximal stomach at any time point in the study), and the distal volume (the highest activity value in the distal stomach at any time point in the study. Gastric emptying of an indigestible solid meal was assessed by calculating gastric clearance of radio‐opaque markers. Results: Sildenafil did not change total gastric emptying or gastric clearance of radio‐opaque markers. It shortened the proximal T_1/2, decreased proximal volume, and significantly increased distal volume. Conclusion: Sildenafil alters the intragastric distribution of food rather than causing gastric stasis.     

The effect and mechanism of action of capsaicin on gastric acid output

Background  Capsaicin has beneficial pharmacological properties, such as the ability to improve appetite and digestion. However, capsaicin has been reported to suppress gastric acid output, but to increase secretion; no consensus as to its effects on gastric acid output has been reached, and the underlying mechanisms remain to be elucidated. Methods  Rat gastric lumen was perfused with capsaicin. Basal acid output and gastric acid secretion stimulated by vagal nerve activation and bethanecol, a muscarinic receptor agonist, were measured. After intravenous infusion of calcitonin gene-related peptide (CGRP), the measurements were repeated. The secretion of gastrin, somatostatin, and histamine was measured in isolated vascularly perfused rat stomach after vagal nerve and bethanecol stimulation, and under the influence of capsaicin. Results  Capsaicin administration had no effect on basal gastric acid output, but inhibited acid secretion resulting from vagal stimulation. Capsaicin had no effect on acid secretion resulting from stimulation with bethanecol. Administration of high-dose CGRP inhibited basal acid output and gastric acid secretion from both vagal nerve and bethanecol stimulation. Low-dose CGRP inhibited gastric acid secretion because of vagal stimulation, but had no effect on basal secretion or acid secretion following stimulation with bethanecol. Capsaicin administration inhibited the stimulated gastrin and histamine secretion and reversed the suppression of somatostatin secretion mediated by vagal stimulation. However, capsaicin had no effect on stimulated gastrin secretion, suppression of somatostatin secretion, or stimulated histamine secretion because of bethanecol. Conclusions  Capsaicin inhibited gastric acid output, and the mechanism underlying this effect appears to involve vagal nerve inactivation.     

Calcitonin gene-related peptide: a potent and selective stimulator of gastrointestinal somatostatin secretion

Calcitonin gene-related peptide (CGRP) exists in nerves throughout the gastrointestinal tract and pancreas, and exogenous CGRP has been reported to inhibit many endocrine and exocrine secretions of the gut and pancreas. Because somatostatin also has widespread inhibitory actions and because both gut and pancreatic somatostatin secretion may be under peptidergic control, we examined the influence of CGRP on circulating levels of somatostatin-like immunoreactivity (SLI) and on hormone output from the duodenal lobe of the dog pancreas in situ. Intravenous infusion of human CGRP in anesthetized dogs increased arterial SLI in a dose-dependent manner. During iv infusion of CGRP at 500 pmol/min, the increment of circulating SLI (change at 20 min, +175 +/- 24 fmol/ml) was composed of nearly equimolar amounts of SLI-14 and SLI-28, suggesting an effect of CGRP on both gastric and intestinal somatostatin secretion. The effect of iv CGRP (500 pmol/min) on arterial SLI exceeded those of iv CCK-8 (440 pmol/min), iv isoproterenol (10 nmol/min), and intragastric administration of acidified liver extract. In contrast, salmon calcitonin (500 pmol/min, iv) was without effect. CGRP did not stimulate pancreatic SLI output when infused iv (500 pmol/min) or when infused directly into a pancreatic artery (5 pmol/min). The pancreatic infusion of CGRP decreased insulin output slightly (change at 20 min, -21 +/- 8%), but did not affect glucagon output. We conclude that CGRP is a most effective yet selective stimulator of gastrointestinal somatostatin release, with little influence on islet function. We suggest that exogenous and possibly endogenous neuronal CGRP could exert inhibitory effects on gastrointestinal function via the release of somatostatin.     

Effects of posture on the physiology of gastric emptying: A magnetic resonance imaging study

Objective. Gastric contents empty from the stomach despite frequent changes in body position. The mechanism that maintains gastric emptying independent of position is poorly understood. The aim of this study was to determine the effects of body position on gastric emptying and motor function. Material and methods. Twelve volunteers were investigated in seated position (SP) and upside-down position (UDP) after ingestion of 300 ml water. Magnetic resonance imaging provided a non-invasive assessment of gastric emptying and volumes, intragastric distribution and peristaltic function. Results. A marked difference in distal/proximal intragastric distribution between UDP and SP was present (7% versus 40%; p?0.01). Gastric-emptying time was similar but emptying pattern was linear in UDP and exponential in SP. Peristalsis was slower in UDP than SP (2.75 versus 2.96 min^?1; p?0.01), but no correlation was found between peristaltic frequency and the rate of gastric emptying in either position. Postprandial volume response (gastric relaxation) was greater in UDP than SP (280 versus 250 ml; p?0.05). A correlation was found between gastric relaxation and gastric-emptying time in SP (r²=0.46) but not in UDP. Conclusions. The stomach maintains the rate of gastric emptying despite radical changes in body position and intragastric distribution of gastric contents. In SP, hydrostatic pressure (modulated by gastric tone) dictates the gastric emptying. In UDP, gastric emptying also appears to be mediated by continuous adaptation of gastric tone. These findings provide support for the hypothesis that the mechanism of gastric emptying resembles a “pressure pump” rather than a “peristaltic pump”.     

Increased intragastric acid-resistant lipase activity and lipolysis in pancreatic steatorrhoea due to cystic fibrosis.

We measured gastric lipase activity and lipolysis in postprandial gastric samples from 10 adults with steatorrhoea due to cystic fibrosis (CF) and from 10 healthy volunteers of similar age and sex. Gastric samples were aspirated for 2 h following a meal consisting of emulsified long-chain triglyceride. Mean acid-resistant lipase activity was twice as high in CF patients as in controls (596 vs. 299 nmol/ml/min fatty acid released; p = 0.028 for area under the curve). Lipolysis rose from 5 to 10% during the postprandial period in CF patients, compared with a constant 5% in controls (p = 0.036 for area under the curve). We conclude that, in healthy adults, lipolysis of long-chain triglyceride starts in the stomach, while in adults with pancreatic steatorrhoea due to CF, gastric lipase activity and intragastric lipolysis are increased, perhaps in compensation for pancreatic insufficiency.     

Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: Central and peripheral mechanisms

Abstract The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin-releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E₂ (PGE₂). Prostaglandin E₂ action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE₂ and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP.     

大鼠幽门区降钙素基因相关肽与胆汁返流的关系

目的探讨降钙素基因相关肽（CGRP）及其拮抗剂（h-CGRP8—37）对正常和应激情况下大鼠胃内胆汁反流的影响。方法SD大鼠65只，实验分三部分：第一部分大鼠20只随机分为四组：对照组、CGRP低、中和高剂量组各5只，分别腹腔注射生理盐水（1ml）和CGRP（10μg／kg 1ml）、CGRP（30μg／kg 1ml）和CGRP（30μg／kg1ml），0．5h后处死，取胃液测胆汁酸（TBA）浓度。第二部分大鼠30只随机分为二组：应激组和h-CGRP8—37组各15只。从浸入水中开始取2、4、6h共3个时段，每个时段各5只。取胃液测TBA浓度。第三部分大鼠15只，分为对照组、应激即刻组（从应激开始，4小时应激结束）和应激后2h组各5只，测胃液TBA浓度，并用免疫组化SP法检测胃幽门区CGRP神经元阳性反应产物（CGRP—ir）的平均光密度变化。结果正常大鼠在腹腔注射不同剂量CGRP0．5h后胃内胆汁酸浓度明显增高；经幽门局部给予CGRP拮抗剂能显著降低应激性溃疡大鼠在2、4、6h三个时段的胃内胆汁返流；免疫组化显示应激性溃疡大鼠胆汁返流增加时，胃幽门区CGRP免疫反应阳性物质活性降低。结论CGRP能促进胃内胆汁酸反流，CGRP参与了幽门括约肌舒张功能的调控。     

Volume accommodation by distension of gastric fundus (rabbit) and gastric corpus (cat)

In attempts to identify the structures of the proximal stomach responsible for volume accommodation, the dimensions of a herbivore (rabbit) were compared to those of a carnivore (cat) stomach at various degrees of filling. The total gastric surface area was similar in both species, but the proximal stomach of cats consisted primarily of the segment between the incisura angularis and the cardia (gastric corpus), while the proximal stomach of the rabbit was represented largely by the true fundus (segment orad to cardia). In both species, the muscle coat of the proximal stomach was thinner than that of the distal stomach, but this difference was more prominent in rabbits than in cats. In both species, the length and the angulation of the lesser curvature were little affected by filling of the stomach. Most length increases of the greater curvature occurred proximal to the cardia in the rabbit and proximal to the incisura angularis in the cat. Filling the stomach increased the length of the gastric circumference more steeply in the cat than in the rabbit. In both species, the stomachs shortened in their longitudinal axis in response to a drug that excites gastric smooth muscle (carbachol). A drug that inhibits gastric smooth muscle (isoproterenol) gave the stomach a more elongated shape. Cat stomachs ruptured at higher volumes and intragastric pressures than rabbit stomachs. In the cat, volume accommodation takes place in the transverse axis of the stomach, and parallel to the circular muscle fibers of the gastric corpus. In the rabbit, volume unfolds the gastric fundus in the longitudinal and transverse axes in parallel to the radiating course of the oblique muscle fibers.