Effect of gastrin on electrical activity of antrum and duodenum of dogs.
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Biomedical subjects
Publications and source records attributed to C F Code.
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The effects of two exposures of the gastric mucosa to either 10 mM taurocholic acid (TcA) or 20% ethanol, both in 150 mM HCl, on transmucosal potential difference (PD) and net fluxes of H+, Na+, and K+ ions have been tested in the rat. The interval between exposures was 30 min. The results demonstrated that the first exposure of the gastric mucosa, either to TcA or to ethanol, reduced the net fluxes of H+, Na+, K+ and the change in transmucosal PD induced by the second exposure, indicating an increased resistance of the mucosa to the barrier breaking effects of TcA or ethanol.
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The study was designed to determine whether the special Na+--H+ barrier function of the gastric mucosa is present in the mucosa of the small bowel and whether a gastric mucosal barrier breaker (hexanoic acid) would accelerate the fluxes of sodium in duodenum-jejunum and ileum as in the stomach. The observations were made in healthy conscious dogs with Thiry-Vella fistulae of the small bowel or Heidenhain pouches of the gastric corpus. These barrier characteristics of the stomach were completely absent in the small intestine where bidirectional Na fluxes were 5--10 times greater than in the stomach and were not accelerated by hexanoic acid as they were in the stomach. A comparison was made between the rates of absorption of hexanoic acid, sodium hexanoate, and HCl from the pouches and fistulae. The lipid-soluble fatty acid was transported at all sites more rapidly than its water-soluble sodium salt. In the stomach and ileum the H+ of HCl and sodium hexanoate were absorbed at similar slow rates. The duodenal-jejunal mucosa, however, transported H+ at rates nearly identical to those of hexanoic acid. In our tests HCl was not neutralized in duodenal contents while large quantities were neutralized in the contents of ileum.
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In 6 (10 to 12 kg) mongrel female dogs, silver electrodes for recording electrical activity and for pacing of pacesetter potentials (PP) were implanted on the stomach and duodenum and a catheter for intraluminal instillations was inserted into the duodenum. Beginning 2 weeks after operation, electrical recordings were made intermittently from the fasted, conscious dogs with no pacing and during pacing of the PP in the proximal and in the distal duodenum. A suspension of BaSO4 injected into the unpaced duodenum and observed cinefluoroscopically was swept quickly from the duodenum into the jejunum; little or none passed orad into the proximal duodenum, and BaSO4 rarely entered the stomach. Only 1 to 3% of a duodenal infusate of 154 mM NaCl with [14C] polyethylene glycol (2 ml per min) appeared in the stomach after 15 min. The results during proximal duodenal pacing were the same as with no pacing. However, distal duodenal pacing, which reversed the direction of propagation of the duodenal PP's, caused duodenal-gastric reflux of BaSO4 in every dog and forced about 30% of the duodenal infusate into the stomach during fasting and during gastric emptying of 400 ml of 154 mM NaCl; at the same time, the rate of emptying of the gastric instillate was slowed about 25%.
Total 14C activity in juice secreted by gastric pouches of six dogs and seven isolated canine stomachs was determined in response to intravenous and intra-arterial infusions of histamine and [14C]histamine. The proportions of 14C attributable to histamine, Nalpha-methylhistamine (NalphaMeH), Nalpha,Nalpha-dimethylhistamine (NalphaNalphaMe2H), N-telle-methylhistamine (NtauMeH), imidazole acetic acid (ImAA), N-methylimidazole acetic acid (NtauMeImAA), acetylhistamine (AcH), and histaminol (HOH) were defined using thin-layer chromatography. Similar estimates were made at the end of infusions on blood, gastric mucosa, and gastric muscle. Methylation was the major, or sole, route of metabolism of histamine in the gastric mucosa, and the major product was inactive NtauMeH. Small quantities of the active NalphaMe derivatives, particularly NalphaNalphaMe2H, were identified in both the juice and mucosa. Little or no ImAA, NtauMeImAA, AcH, and HOH were present in juice from isolated stomachs while they did occur in the juice from intact dogs, demonstrating they are extragastric metabolites of histamine. A major mucosal function of methylation of histamine is inactivation, although NalphaMe derivatives formed may play a role in the secretagogue action of histamine.
Prostaglandins (PGE1, PGE2, PGA1) and histamine have opposing effects on gastric HCl secretion, but we found that both stimulate adenylate cyclase activity in cell-free membrane preparations of guinea pig gastric fundic mucosa. The stimulatory effect of prostaglandins was found in this study to be specific and dose-dependent over a concentration range from 10(-7) to 10(-4) M. In similar preparations from antral regions of guinea pig gastric mucosa, the adenylate cyclase was stimulated only by PGE1, PGE2, and PGA1 and not by histamine. Maximum stimulating doses of PGE1, PGE2, or PGA1, and of histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. Metiamide, a histamine H2-receptor antagonist, inhibited the stimulation of fundic mucosa adenylate cyclase by histamine but did not interfere with the stimulation by prostaglandins. Cyclic AMP phosphodiesterase activity of guinea pig gastric mucosa was unaffected by PGE1 and PGE2 or by histamine, and was slightly depressed by PGA1. These results indicate that histamine and prostaglandins stimulate two different adenylate cyclase systems both present in guinea pig gastric mucosa tissue. Therefore, the known inhibitory effect of prostaglandins on gastric acid secretion is not related to the interference with the stimulation of the histamine H2-receptor-sensitive adenylate cyclase complex by histamine nor do prostaglandins accelerate cyclic AMP breakdown by cyclic AMP phosphodiesterase to reduce cyclic AMP levels.
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1. Szurszewski (1969) described a cyclic recurring, caudally migrating band of intense action potential activity, the activity fromt, in the small bowel of dogs fasted 18-21 hr. The finding has been confirmed by Carlson, Bedi & Code (1972) and by Grivel & Ruckebusch (1972). The objectives of the present study were to extend these observations first by indentifying the full sequence of myo-electric events in the stomach and small bowel of healthy conscious dogs fasted for 24-48 hr and for longer periods and second by determining the effect of ingestion of mild and of saline solution on the complex and the role of gastric distension in their action. 2. Under surgical anaesthesia, silver-silver chloride electrodes were implanted on the serosal surface of the stomach and small bowel of seven dogs, and recordings of electric activity were started when the dogs had recovered. One hundred and nine interdigestive complexes were studied in detail in five of the dogs during period ranging from 5 to 14 months. All observations were made while the dogs were healthy, conscious, and fasted. 3. The period of intense action potential activity, the activity frot or band, was found to be one phase of a cyclic-recurring sequence of changes in action potential activity. The entire sequence, composed of four phases, occured almost simultaneously in the stomach and duodenun and then migrated distally in sequence over the entire small bowel. As one cycle terminated in the distal ileum, another had started in the stomach and duodenum, and this cyclic recurrence continued during fasts of 4 and 5 days. 4. The cycles of the interdigestive complex tended to recur at the same time each day in three of the dogs. The mean periods of the cycles ranged from 90 to 114 min, and the mean time of their propagation from stomach to terminal ileim ranged from 105 to 134 min. The mean velocity of the activity fronts (phase III of the cycles) was 5-7-11-7 cm/min in the orad portion of the small bowel and 0-9-2-5 cm/min in the distal half. The mean calculated length of the activity front diminished from a range of 42-62 cm in the duodenum to 5-10 cm in the ileum. 5. Intragastric instillation of 400 ml. milk always interrupted the complex present in the bowel at the time of instillation and usually suppressed the next, whereas 400 ml. saline solution interrupted the complex present in the bowel only at the time of instillation. Distension of the stomach with a ballon always suppressed the interdigestive complex in the stomach and duodenum but sometimes failed to interrupt its migration along the bowe.
In 10 conscious, fasted dogs with electrodes chronically implanted on the intestine, current pulses (8 mA, 50 ms) at frequencies the same as, or faster than, that of the natural intestinal pacemaker always entrained pacesetter potentials (PP) along the proximal frequency plateau, but not along the distal frequency gradient. As duodenal PP's were paced faster, the proximal plateau shortened by orad extension of the distal gradient. Entrained PP's propagated orally and aborally. Their velocity slowed caudally while varying inversely with their frequency. After midduodenal transection had reduced the frequency of the natural PP's distal to the cut, pacing entrained PP's in all areas of the bowel and restored the proximal plateau and distal gradient. But no area could be paced faster than before transection. PP's were not propagated across sites of transection. A digital computer model of coupled relaxation oscillators gave similar results. We conclude that the frequency of the natural pacemaker and the declining gradient of maximal driven frequency determine the frequency pattern of the small intestinal PP.
Three bears were studied under conditions of (1) no food but access to water for 2 weeks and (2) no food or water for 3 weeks. During starvation in summer, the bears could not inhibit the net production of urea but used lean body mass; when denied access to water as well, the bears became dehydrated and azotemic. Urea was continuously formed and degraded in the winter. Arginase activity in liver increased in winter sleep; hepatic steatosis and inflammatory reactions were also noted. The urinary bladder readsorbed labeled urea and D20 in winter; the rate of absorption of urea was equal to the rate of excretion of it into the bladder. The ability to preserve lean body mass during winter sleep apparently is a special mechanism associated with the induction of winter sleep. Bears cannot duplicate this feat during summertime starvation. In winter sleep, urea is formed and degraded but the nitrogen produced is conserved in some manner that maintains the total nitrogen pool constant. The urinary bladder plays a central role in maintaining the state of winter sleep by absorbing water and solute at a rate equal to their entry into the urinary bladder.
In healthy, consious, intact fasted dogs, infusion of pentagastrin interrupted the interdigestive myoelectric complex in the stomach and small bowel and replaced it with activity that closely resembled that seen after feeding. After bilateral transthoracic vagotomy, pentagastrin infusion still interrupted the complex but now, in addition, upon stopping the pentagastrin, a premature activity front (phase III) of the complex was also followed by a reduction in the temporal regularity of the cycles of the complex. Fewer cycles per 10 hr occurred in most dogs after vagotomy, and the complexes were not as regularly interrupted by feeding a small meal of 50 g of meat as they had been before vagotomy. The results indicate that both neural and humoral influences have a role in controlling the interdigestive motor complex of dogs.
This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid "bolus" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr.
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