gastrins and Ischemia

Topics: Bile; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastritis; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Ischemia; Permeability; Stomach Ulcer

Histamine in the rat stomach resides in enterochromaffin-like (ECL) cells and mast cells. The ECL cells are peptide-hormone-producing endocrine cells known to release histamine and chromogranin-A-derived peptides (such as pancreastatin) in response to gastrin. Ischemia (induced by clamping of the celiac artery or by gastric submucosal microinfusion of the vasoconstrictor endothelin) mobilizes large amounts of ECL-cell histamine in a burst-like manner. This report examines the ECL-cell response to ischemia and compares it with that induced by gastrin in rats. Arterial clamping (30 min) and gastric submucosal microinfusion (3 h) of endothelin, vasopressin, or adrenaline caused ischemia, manifested as a raised lactate/pyruvate ratio and mucosal damage. Whereas microinfusion of gastrin released both histamine and pancreastatin, ischemia mobilized histamine only. The mucosal concentrations of histamine and pancreastatin, the number and immunostaining intensity of the ECL cells, and the ultrastructure of the ECL cells were unchanged following ischemia. The long-term effects of ischemia and reperfusion (60-90 min) on gastric mucosa were examined in rats treated with the proton pump inhibitor omeprazole for 4 days. The activity of the ECL cells was suppressed (reflected in low histamine-forming capacity) but returned to normal within 1 week, illustrating the ability of the ECL cells to recover. We suggest that ischemia mobilizes cytosolic ECL-cell histamine without affecting the storage of histamine (and pancreastatin) in the secretory organelles and without causing lasting ECL-cell impairment.

Topics: Animals; Cell Compartmentation; Chromogranin A; Cytosol; Endothelins; Enterochromaffin-like Cells; Epinephrine; Female; Gastric Mucosa; Gastrins; Histamine; Histamine Release; Ischemia; Pancreatic Hormones; Rats; Rats, Sprague-Dawley; Secretory Vesicles; Vasopressins

Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.

Topics: Animals; Capsaicin; Dose-Response Relationship, Drug; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Ghrelin; Injections, Intraperitoneal; Injections, Intraventricular; Ischemia; Male; Neurons, Afferent; Protective Agents; Rats; Rats, Wistar; Recombinant Proteins; Stomach; Stomach Ulcer; Vagus Nerve

Oxytocin treatment in rats induces long-lasting antistress and growth promoting effects. This study investigated whether prolyl-leucyl-glycinamide (PLG) (the c-terminal tripeptide of oxytocin) or tocinoic acid (the ring structure of oxytocin) could induce some of these effects in male rats. For this purpose, PLG (2 or 10 mg/kg, s.c.) or tocinoic acid (1 mg/kg, s.c.) was administered to rats once a day for 3 or 5 days. Blood pressure, heart rate, spontaneous motor activity, nociceptive thresholds, and the survival of ischaemic musculocutaneous flaps were measured. In addition, endogenous oxytocin levels and plasma levels of some hormones known to be influenced by oxytocin were determined. PLG (2 mg/kg, s.c., but not 10 mg/kg, s.c.) decreased diastolic blood pressure (p<0.05) and locomotor activity (p<0.05). PLG (10 mg/kg, s.c.) decreased gastrin (p<0.05) and endogenous oxytocin levels in plasma (p<0.01). Tocinoic acid decreased locomotor activity (p<0.05), but did not affect any of the other parameters measured. In conclusion, this study showed that both PLG and tocinoic acid decrease locomotor activity. In addition, PLG also induced some other effects similar to those induced by oxytocin treatment but when administered in high doses it decreased oxytocin levels.

Topics: Animals; Behavior, Animal; Blood Pressure; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Gastrins; Heart Rate; Ischemia; Male; Motor Activity; MSH Release-Inhibiting Hormone; Oxytocin; Pain Threshold; Rats; Rats, Sprague-Dawley; Surgical Flaps

The mechanism responsible for gastric colonization in critically injured ICU patients remains to be fully elucidated. Moreover, the effects of gut ischemia/reperfusion (I/R) injury on gastric function are unclear. It was our hypothesis that gut I/R injury would cause gastric dysfunction.. Rats were anesthetized and, via laparotomy, the superior mesenteric artery (SMA) was clamped at its aortic origin for 45 min followed by clamp removal. Rats were allowed to awaken and then killed after 6 h of reperfusion. Control rats underwent laparotomy with SMA isolation. Stomachs were removed, gastric fluid was aspirated, and the volume, pH, and protein, bicarbonate, and glucose contents were determined. Serum and antral mucosa were prepared for gastrin radioimmunoassay and the glandular mucosa was assessed for morphologic injury.. SMA I/R injury caused significant accumulation of gastric luminal fluid that was alkaline and rich in protein, glucose, and bicarbonate content when compared with sham controls. SMA I/R injury also caused gastric surface epithelial cell injury and significantly increased serum and antral gastrin levels. In additional rats, gut I/R injury inhibited basal acid secretion and blunted the acid secretory response to pentagastrin.. This study demonstrated for the first time that small intestinal I/R injury causes significant gastric dysfunction. The findings suggest that this type of injury, a frequent occurrence in critically injured ICU patients, may predispose patients to gastric colonization due to stasis and loss of the natural bactericidal effects of gastric acid.

Topics: Animals; Female; Gastric Acid; Gastric Mucosa; Gastrins; Intestine, Small; Ischemia; Rats; Reperfusion Injury; Stomach

Plasma levels and renal uptake of gastrin were determined in ten dogs submitted to complete liver devascularization in order to induce an acute liver failure. Renal function was evaluated by renal plasma flow (RPF) and glomerular filtration rate (GFR) determinations. Liver devascularization was obtained by end-to-side porto-caval shunt (PCS) followed by temporary clamping of the hepatic artery. PCS alone did not affect renal function and renal ability to remove gastrin; after hepatic ischemia, both RPF, GFR and renal extraction of gastrin showed an abrupt decrease. At the end of the period of hepatic ischemia 5 dogs were submitted to glucose infusion, in consideration that: i) glucagon is able both to affect gastrin release and renal hemodynamics, and ii) hypoglycemia that develops after liver failure releases elevated amounts of glucagon. The renal handling of gastrin was not related to glucagon plasma levels, though the higher gastrin levels occurred at the lower glucagon concentrations. These data suggest that in acute liver failure there is a striking decrease of the renal clearance of gastrin associated with the impairment of kidney function. Furthermore, in this pathological condition plasma gastrin levels are affected by blood glucose concentrations through its effect on plasma glucagon levels.

Topics: Acid-Base Equilibrium; Animals; Blood Glucose; Dogs; Gastrins; Glucagon; Hemodynamics; Ischemia; Kidney; Liver; Male