Quantitative analysis of the role of cholinergic, gastrin, and histamine regulatory mechanisms of pepsinogen production in the stomach of narcotized rats

Abstract

Pepsinogen secretion in the intraluminally perfused stomach of narcotized rats was induced by electrical stimulation of the vagus nerve or intravenous injection of pentagastrin. Blockade of histamine H 2 receptors inhibited pepsinogen production induced by vagal stimulation by 35%, but caused only a 13% decrease in pentagastrin-stimulated pepsinogen secretion. Key Words: pepsinogen; vagus; pentagastrin; histaminePractically in all mammals, vagal cholinergic and gastrin effects on parietal cells of the stomach are mediated by histamine-producing cells [4]. Chief cells of the gastric mucosa producing pepsinogen are evolutionary similar to parietal cells [3,10] and functionally depend on their state. However, of mechanisms secretion, nervous and endocrine regulation in these cells differ considerably [5,6,11]. The data on the involvement of main secretagogues in the regulation of pepsinogen production are contradictory due to species specificities and peculiarities of experimental models [9,12]. The role of histamine in mediating vagal and gastrin effects on chief cells of the stomach remains unclear. Here we evaluated the role of cholinergic, gastrin, and histamine mechanisms in the regulation of pepsinogen secretion in the stomach of narcotized rats. MATERIALS AND METHODSExperiments were performed on 42 male SpragueDawley rats weighing 309• g and kept at 20+1~ under a 12-h light/dark schedule and ad libitum food supply (Rappolovo R50258-92). One day before operation, the animals were deprived of food, but had free access to water.The rats were narcotized with intraperitoneal injection of choral hydrate and urethane (800+ 100 mg/kg, Sigma). Isotonic NaC1 containing 3 mM NaHCO 3 and 2% glucose was administered intravenously (1 ml/h) to prevent acidosis and dehydration. The animals were heated on a temperature-controlled table with incandescent lamp. Heart rate (HR), blood pressure (BP), and rectal temperature were measured.After tracheotomy, catheterization of the right femoral artery and vein, and median laparotomy were carried out subdiaphragmatic vagotomy, gastric sympathectomy, and ligation of the left adrenal gland were conducted if required. The stomach was perfused with isotonic NaC1 at a flow rate of 0.7 ml/min, 37~ pH 6.0, and 0 mm Hg. The solution was administered through a catheter and removed via a perforated polyethylene tube introduced through a duodenal section into the pylorus. The peripheral end of the left subdiaphragmatic vagus nerve was demyelinated and stimulated with rectangular pulses (6 V, 1 msec, 8 Hz) delivered through silver electrodes for 10 min.Perfusate samples were taken at 15-min intervals using a fraction collector (LKB). Pepsinogen concen-0007-4888/00/0001-7525.00 9Kluwer Academic/Plenum Publishers