Modulation by nitric oxide of gastric acid secretion in toads

Nitric oxide (NO) is a novel chemical messenger that mediates a variety of biological actions. This study was undertaken to investigate the effects of NO on parietal cell function. The rate of [³H]arginine conversion to [³H]citrulline, a parameter of NO synthase activity, and NO formation (as NO^?₂), were inhibited by the NO synthase inhibitor, N ^G-nitro- L -arginine methyl ester ( L -NAME), in a concentration-dependent manner in the non-stimulated toad gastric mucosa. This range of concentrations of L -NAME provoked stimulation of H⁺ secretion in a similar fashion, which was blocked by L -arginine but not by D -arginine. Pre-treatment with carbachol plus ethylene glycol-bis(β-aminoethyl ether)-N,N,N ′,N ′-tetra-acetic acid (EGTA) prevented the effect of L -NAME on H⁺ secretion and drastically reduced NO synthase activity. L -arginine had an inhibitory effect on H⁺ secretion in non-stimulated and carbachol-stimulated gastric mucosa, which was reversed by L -NAME. Carbachol and pentagastrin, but not histamine, significantly increased NO formation in the toad gastric mucosa. The results suggest that changes in NO synthesis in the gastric mucosa may modulate parietal cell function and that a calcium-dependent mechanism may be involved.     

CATs and HATs: the SLC7 family of amino acid transporters

The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1–4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5–11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system x_c^–) and cationic amino acids plus neutral amino acids (system y⁺L and b^0,+-like). Cotransport of Na⁺ is observed only for the y⁺L transporters when they carry neutral amino acids. Mutations in b^0,+-like and y⁺L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectively.     

Arginine transport in human erythroid cells: discrimination of CAT1 and 4F2hc/y+LAT2 roles

Since arginine metabolites, such as nitric oxide and polyamines, influence the expression of genes involved in erythroid differentiation, the transport of the cationic amino acid may play an important role in erythroid cells. However, available data only concern the presence in these cells of CAT1 transporter (system y⁺), while no information exists on the role of the heterodimeric transporters of system y⁺L (4F2hc/y⁺LAT1 and 4F2hc/y⁺LAT2) which operates transmembrane arginine fluxes cis-inhibited by neutral amino acids in the presence of sodium. Using erythroleukemia K562 cells and normal erythroid precursors, we demonstrate here that arginine transport in human erythroid cells is due to the additive contributions of a leucine-sensitive and leucine-insensitive component. In both cell types, leucine inhibition of arginine influx is much less evident in the absence of sodium, a hallmark of system y⁺L. In K562 cells, N-ethylmaleimide, a known inhibitor of CAT transporters (system y⁺), suppresses only a fraction of arginine influx corresponding to leucine-insensitive uptake. Moreover, in Xenopus oocytes coexpressing 4F2hc and y⁺LAT2, leucine exerts a marked inhibition of arginine transport, partially dependent on sodium, while no inhibition is seen in oocytes expressing CAT1. Lastly, silencing of SLC7A6, the gene for y⁺LAT2, lowers arginine transport and doubles the intracellular content of the cationic amino acid in K562 cells. We conclude that arginine transport in human erythroid cells is due to both system y⁺ (CAT1 transporter) and system y⁺L (4F2hc/y⁺LAT2 isoform), which mainly contribute, respectively, to the influx and to the efflux of the cationic amino acid.     

Kidney amino acid transport

Near complete reabsorption of filtered amino acids is a main specialized transport function of the kidney proximal tubule. This evolutionary conserved task is carried out by a subset of luminal and basolateral transporters that together form the transcellular amino acid transport machinery similar to that of small intestine. A number of other amino acid transporters expressed in the basolateral membrane of proximal kidney tubule cells subserve either specialized metabolic functions, such as the production of ammonium, or are part of the cellular housekeeping equipment. A new finding is that the luminal Na⁺-dependent neutral amino acid transporters of the SLC6 family require an associated protein for their surface expression as shown for the Hartnup transporter B⁰AT1 (SLC6A19) and suggested for the l-proline transporter SIT1 (IMINO^B, SLC6A20) and for B⁰AT3 (XT2, SLC6A18). This accessory subunit called collectrin (TMEM27) is homologous to the transmembrane anchor region of the renin–angiotensin system enzyme ACE2 that we have shown to function in small intestine as associated subunit of the luminal SLC6 transporters B⁰AT1 and SIT1. Some mutations of B⁰AT1 differentially interact with these accessory subunits, providing an explanation for differential intestinal phenotypes among Hartnup patients. The basolateral efflux of numerous amino acids from kidney tubular cells is mediated by heteromeric amino acid transporters that function as obligatory exchangers. Thus, other transporters within the same membrane need to mediate the net efflux of exchange substrates, controlling thereby the net basolateral amino transport and thus the intracellular amino acid concentration.     

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2′,7′-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-β-d-riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.     

Method of studying hydrochloric acid secretion by the isolated gastric mucosa using a two-channel pH-meter

A method of recording the secretion of hydrochloric acid by means of a two-channel system in symmetrical halves of the same area of isolated gastric mucosa is suggested. The system has important advantages over the one-channel method. A special feature of this method is that the effect of various substances on the rate of secretion of H⁺ can be more clearly differentiated and the wastage of animals is substantially reduced. The block diagram of the apparatus for two-channel recording of H⁺ secretion and the design of the four-chamber cuvette are described.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 888–889, July, 1976.     

Urea in gastric juice

Summary In the basal secretion and in the gastric juice after stimulation with 6 µg/kg Pentagastrin in 15 persons a linear reciprocal relationship (r=–0.84) between the concentration of H⁺ and urea was demonstrated. The urea concentration in the non parietal secretion was 32 mg%, which corresponded to the serum urea concentration of 29 mg%. The interception of the dose relationship line was at a H⁺ concentration of 148 mEq/L. From this data it is concluded that urea is not secreted in the parietal secretion, but is excreted in the non parietal secretion in the same concentration as in the extracellular fluid.

---

Zusammenfassung Eine umgekehrte lineare Beziehung zwischen den Konzentrationen von H⁺ und Harnstoff (r=–0,84) konnte in der Nüchternsekretion und der Magensaftsekretion nach Stimulierung mit 6 µg/kg Pentagastrin von 15 Personen nachgewiesen werden. Die Harnstoffkonzentration in der alkalischen Primärsekretion stimmte mit 32 mg% gut mit der Serumharnstoffkonzentration von 29 mg% überein. Der Schnittpunkt der Regressionsgeraden lag bei einer HCl-Konzentration von 148 mval/l. Diese Befunde zeigen, daß Harnstoff nicht in der sauren Primärsekretion, sondern in der alkalischen Primärsekretion mit derselben Konzentration wie im Extracellulärraum sezerniert wird.

     

Effects of glucagon and histamine on human parietal cells

Sincein vivo pancreatic glucagon inhibits gastric acid secretion it was of interest to test its direct effect on human parietal cell functionin vitro by measuring adenylate cyclase (AC) activity and H⁺ production. Cells were isolated from human gastric mucosa obtained at surgery for peptic ulcer. In enriched (75%) parietal cells glucagon and histamine stimulated AC much more effectively than in the parietal cell depleted (15%, 7%) fractions. In contrast basal and histamine-stimulated [¹⁴C] aminopyrine uptake, an indirect measure of parietal cell H⁺ production, was not affected by glucagon. In homogenates of mucosal biopsy specimens 2×10^–7 mol/l glucagon enhanced AC activity by 76% (corpus) and 20% (antrum), respectively; in the same homogenates 10^–4 mol/l histamine caused a stimulation by 161% (corpus) and 38% (antrum). In fundic biopsy specimens glucagon displayed a biphasic concentration response curve with an increase at 10^–10 mol/l (46% above basal AC activity) and a maximum at 2×10^–7 mol/l (97%); histamine elicited the maximal response (192%) at 10^–3 mol/l. Histamine (10^–5, 10^–4, 10^–3 mol/l) and glucagon (10^–10 to 10^–6 mol/l) caused additive stimulation of AC. Ranitidine did not change AC in response to glucagon but abolished the effect of histamine. Our data demonstrate that glucagon stimulates an AC bound to the parietal cells. This response is not blocked by ranitidine suggesting that the glucagon action is mediated by a separate receptor, possibly by a glucagon-receptor. Furthermore we have shown that glucagon in contrast to its effects on AC does not affect H⁺ production. This discrepancy suggests coexistence of two AC systems in the parietal cell: One that is activated via histamine H₂ receptors and which stimulates H⁺ production; another AC is activated by glucagon and is directed towards other, possibly metabolic effects.     

Histidine-stimulated acid secretion in the conscious rat is mediated by amino acid uptake system N

The characteristics of sodium-dependent, histidine-stimulated gastric acid secretion were studied in the conscious gastric-fistulated rat. Intragastric L-histidine, but not glutamine, asparagine, glutamic acid or glycine, stimulated acid secretion. The histidine-stimulated acid secretion was inhibited by the presence of glutamine or asparagine, but not by glutamic acid or glycine. The substitution of lithium for sodium in the gastric perfusate was tolerated. Together with previous data, the results indicate that an N-like amino acid uptake system mediates histidine-stimulated acid secretion in the conscious rat.     

Characterisation of Proton Pump Antibodies and Stomach Pathology in Gastritis Induced by Neonatal Immunisation without Adjuvant

It has previously been reported that neonatal BALB.D2 mice injected with native proton pump antigens without adjuvant develop an irreversible gastritis (Claeys et al, 1997). The ease of inititating gastritis in the neonate stands in contrast with the difficulty in initiating gastritis in adult mice that require repeated immunisation in adjuvant that is reversible following cessation of immunisation (Scarff et al, 1997). In view of these contrasting observations, we set out to ascertain whether we could confirm the observations in neonatal mice as well as further characterise the pathology and the autoantibody response. We found that neonatal gastritis-susceptible BALB/c mice (n=12), immunised with either pig or mouse gastric membranes in the absence of adjuvant, develop gastritis without circulating antibody to parietal cells detected by immunofluorescence, a hallmark of murine and human gastritis (Toh et al, 1997). However, mice immunized with pig gastric membranes (n=6) had circulating antibodies reactive by immunofluorescence to recombinant α and/or β subunit of gastric H⁺/K⁺-ATPase expressed by insect cells (Sfα and Sfβ). Four mice from this cohort with antibodies to Sfβ also had reactivity to gastric H⁺/K⁺-ATPase by ELISA, and 3 immunoblotted the β but not the a subunit of the ATPase. In the cohort of mice immunised with mouse gastric membranes (n=6), four produced antibodies reactive by immunofluorescence to Sfα, two of which were also reactive to Sfβ and one developed antibodies detected by ELISA to gastric H⁺/K⁺-ATPase. However, no members of this cohort had antibodies reactive by immunoblot-ting to either the p or a subunit of the ATPase. In all cases gastritic stomachs were characterised by areas deficient in ribosome-rich zymogenic cells and marked reductions in H⁺/K⁺-ATPase-positive parietal cells. Metaplasia detected by Maxwell stain, as clusters of mucus-producing cells throughout gastric units, were non-reactive to stomach mucin autoantibody suggesting the mucins comprise other and/or aberrant form(s). Compared to our previous observations in adult mice, our present data confirms that gastric autoimmunity is more readily induced in the neonate than the adult. Our data also affirms that while the neonatal immune system can mount a damaging inflammatory cellular immune response to gastric antigens, it develops an altered antibody response.     

An immunocytochemical study of regeneration of gastric epithelia in rat experimental ulcers

We experimentally observed the process of regeneration of gastric mucosal cells in ulcers induced by surgical removal of the fundic mucosa of rats. The techniques utilized were immunocytochemistry, laser confocal microscopy, and transmission electron microscopy (TEM). Routine TEM and PAS reaction were used for parietal cells, chief cells, and mucous cells. As markers of parietal cells, H⁺-K⁺ ATPase, Na⁺-K⁺ ATPase, carbonic anhydrase, and aquaporin 4 (AQP4) were used, and for chief cells pepsinogen was used. Healing process of mucosal defect was as follows. On day 2 after the operation, the single-layered regenerating epithelium (RE) originating from the marginal epithelium of the ulcer extended over the granulation tissue of the ulcer base towards the center. Regenerating glands (RGs) appeared in the ulcer margin. The cells appearing first in the RE were undifferentiated cells that had a high nucleus: cytoplasm ratio and abundant free ribosomes. On day 5, the ulcer was almost filled with RGs. Most cells stained positive for PAS reaction. A few immature parietal cells stained weakly with H⁺-K⁺ ATPase, Na⁺-K⁺ ATPase, carbonic anhydrase, and aquaporin-4 antibodies, and a few immature chief cells stained weakly with pepsinogen antibody were also observed on day 5. On day 10, the ulcer was filled with RGs. The RGs in the periphery of the ulcer stained positive for markers of mature parietal cells and chief cells, whereas the center of the ulcer was composed of immature parietal cells and chief cells. By day 25, the mucosal defect was filled with normal gastric glands formed by maturation of the RGs. The undifferentiated cells that first appeared in the ulcer margin seem to differentiate to special functioning cells of the stomach 5–10 days after ulcer formation.     

Effect of glucagon on adenylate cyclase activity and acid production of isolated human parietal cells

Summary The direct effect of glucagon on human parietal cell function in vitro was tested by measuring adenylate cyclase (AC) activity and H⁺ production in homogenates of human gastric mucosa obtained during surgery or at biopsy. Cells isolated from mucosa obtained during surgery showed an increase in AC with histamine and glucagon. In parietal cell enriched fractions (75%) glucagon and histamine stimulated AC much more effectively than in parietal cell depleted fractions (15% and 7%). In contrast, glucagon did not affect basal or histamine stimulated¹⁴C amino pyrine uptake.In homogenates of mucosal biopsy specimens 2×10^–7 mol/l glucagon enhanced AC activity by 76% (corpus) and 20% (antrum). In the same homogenates 10^–4 mol/l histamine caused a stimulation by 161% (corpus) and 38% (antrum). In fundic biopsy specimens glucagon displayed a biphasic concentration response curve with an increase at 10^–10 mol/l (46% above basal AC activity) and a maximum at 2×10^–7 mol/l (97%). Histamine elicited the maximal response (192%) at 10^–3 mol/l. Increasing histamine and glucagon concentrations caused additive stimulation of AC. Ranitidine did not change AC in response to glucagon but abolished the effect of histamine. Data suggest that the glucagon action is mediated by separate (glucagon?) receptors. As H⁺ production was not affected by glucagon, the coexistence of two AC systems in the human parietal cell is postulated: One that is activated via histamine H₂-receptors and which stimulates H⁺ production; another that is activated by glucagon and is directed towards other, possibly metabolic effects.Abbreviations AC Adenylate cyclase - cAMP Cyclic adenosine monophosphate - ATP Adenosine triphosphate Supported by grants from the Deutsche Forschungsgemeinschaft Mi 170/2-2Dedicated to Prof. Dr. F. Krück on the occasion of his 65th birthday     

Increased parietal cell sensitivity after chronic treatment with ranitidine in the conscious cat

The sensitivity of histamine H₂ receptors of the gastric mucosa after one month treatment with ranitidine, administered daily (5 mg/kg i.m.), was checked in 5 conscious cats provided with gastric fistula. Basal acid secretion as well as the acid response to the H₂ agonist dimaprit (60 μg/kg/hr) were studied before and at different periods after cessation of ranitidine treatment (1, 3, 7 and 14 days). Control experiments were carried out in 5 gastric fistula cats which received daily physiological saline for one month. Basal acid secretion in treated animals increased significantly (P<0.05) from 0.04±0.002 to 0.24±0.05 mEq H⁺/10 min. Also the response to dimaprit increased significantly (p<0.05) from 0.49±0.08 to 0.86±0.12 mEq H⁺/10 min. Seven days after cessation of treatment, both basal and stimulated secretion returned to pretreatment levels. In control cats no significant difference was noticed in basal and stimulated secretion at the beginning and at the end of the study.     

Histamine-1 receptors do not directly modulate canine gastric acid secretion

The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of the H₁-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H₁-receptor agonist on dimaprit stimulated gastric secretion. Although H₁-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H₂-agonist), suggesting that the enhanced gastric acid secretion after administration of H₁-receptor antagonist is not because of the inhibition of histamine receptor at the gastric fundus. In addition, 2 doses of H₁-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H₁-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.     

Effect of amiloride on arachidonic acid and histamine release from rat mast cells

The effect of a putative Na⁺/H⁺ exchange inhibition on histamine and [¹⁴C]arachidonic acid ([¹⁴C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na⁺. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na⁺/H⁺ exchange in rat mast cell secretion is discussed.     

Histamine-1 receptors do not directly modulate canine gastric acid secretion

The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of H₁-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H₁-receptor agonist on dimaprit stimulated gastric secretion. Although H₁-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H₂-agonist), suggesting that the enhanced gastric acid secretion after administration of H₁-receptor antagonist is not becacuse of the inhibition of histamine receptor at the gastric fundus. In addition, two doses of H₁-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H₁-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.     

Effects of splanchnic nerve stimulation and of clonidine on gastric and duodenal HCO-3 secretion in the anaesthetized cat

Experiments were performed on chloralose-anaesthetized cats with ligated adrenals. The vagal and splanchnic nerves were cut and arranged for peripheral electric stimulation. The gastric lumen was perfused with isotonic saline and gastric H⁺ and HCO₃^-secretions were calculated from pH/pCO₂ measurements in the perfusate. Gastric motility was recorded as changes in hydrostatic pressure in the perfusion circuit. Mucosal HCO₃^- secretion into the duodenum was monitored in situ by pH-stat titration. Vagal stimulation (10 Hz for 10 min) increased gastric and duodenal HCO₃^- secretions, as well as gastric motor activity and H⁺ secretion. Splanchnic nerve stimulation (10 Hz for 10 min) did not affect gastric H⁺ and HCO₃^- secretions, but tended to decrease gastric motor tone and basal duodenal HCO₃^- secretion. Splanchnic nerve stimulation simultaneously with vagal stimulation inhibited gastric contractions and the rise in gastric H⁺ and duodenal HCO₃^- secretions observed in response to vagal stimulation alone, but had little effect on the rise in gastric HCO₃^- secretion. However, such vago-splanchnic stimulation in the presence of the α₂^- adrenoceptor blocker yohimbine induced gastric contractions, H⁺ secretory and duodenal HCO₃^- secretory responses with magnitudes similar to those induced by vagal stimulation alone, whereas the gastric HCO₃^- secretory response was larger than by vagal stimulation alone. The α₂^-adrenoceptor agonist clonidine (50 μg kg^-1 h- ¹ , i.v.) inhibited the gastric contractions and increases in gastric and duodenal HCO₃^- secretion in response to vagal stimulation, but did not influence vagal stimulation of gastric H⁺ secretion. The results suggest the existence of a peripheral sympatho-inhibitory action on gasmc and duodenal HCO₃^-secretion involving α₂^-adrenoceptors. Also splanchnic neural stimulatory effects on gastric and duodenal HCO₃^- secretion may exist.     

The localization of a histamine H2-receptor adenylate cyclase system in canine parietal cells and its inhibition by prostaglandins

A method is described for the preparation of parietal cell-enriched suspensions from dog gastric mucosa. Histamine and E type prostaglandins produce an elevation of cyclic AMP concentration in mixed cell preparations. Parietal cell-rich fractions respond to histamine but only weakly to prostaglandins whilst in fractions virtually free from parietal cells the converse is observed. Prostaglandins which are good antisecretory agents, PGE₁, PGE₂ and 16,16 dimethyl PGE₂ are potent inhibitors of the histamine elevation of cyclic AMP in parietal cell-rich fractions, whilst PGF₂ shows 1% of their potency. The experiments described support the view that histamine stimulates gastric acid secretion by excitation of an H₂-receptor adenylate cyclase system in the plasma membrane of the parietal cell and that acid secretory inhibition by prostaglandins is a result of inhibition of that system.     

Der Einfluß akuter Hypermagnesiämie auf die durch Methylxanthine (Theophyllin) stimulierte Säure-, Elektrolyt- und Pepsinogensekretion des menschlichen Magens

Zusammenfassung Akute Hypermagnesiämie hemmt die basale als auch die durch Calcium, Pentagastrin und Gastrin stimulierte Säuresekretion des menschlichen Magens. An 12 Probanden wurde bei 14 quantitativen Magensekretionsanalysen der Einfluß akuter Hypermagnesiämie auf die durch Methylxanthine (Theophyllin) intracellulär stimulierte Säuresekretion und auf die Elektrolyt- und Pepsinogensekretion untersucht. Magnesium hemmt die Sekretion von H⁺, Cl^–, K⁺- und Na⁺-Ionen und von Pepsinogen. Die Konzentration der Cl^–-und Na⁺-Ionen und des Pepsins blieben statistisch unverändert. Die Konzentration der H⁺-Ionen nahm dagegen in der fünften 15 min-Portion signifikant zu und die der K⁺-Ionen in der achten 15 min-Portion signifikant ab. Die möglichen Angriffspunkte des Magnesiums in der Stimulationsreihe: first messenger — target tissue — second messenger werden diskutiert.

---

Influence of acute hypermagnesemia on methylxanthine (theophylline) -stimulated gastric acid, electrolyte, and pepsinogen secretion in man

Summary Acute hypermagnesemia inhibits human gastric acid secretion stimulated by calcium, pentagastrin and gastrin. 14 quantitative gastric secretion analyses were performed in 12 subjects to study the influence of acute hypermagnesemia on gastric acid secretion intracellularly stimulated by methylxanthines (theophylline). The influence on the stimulated electrolyte and pepsinogen secretion was also studied. Hypermagnesemia inhibits H⁺, Cl^–, K⁺, Na⁺ and pepsinogen secretion. Cl^–, Na⁺ and pepsin concentrations remained unaltered. There was a significant increase in H⁺ in the fifth 15 min portion, and a significant decrease in K⁺ concentrations in the eight 15 min portion, respectively. The possible hypotheses for the mechanism of action of hypermagnesemia in the stimulation series are discussed: first messenger—target tissue second messenger.

---

---

Mit Unterstützung des Landesamtes für Forschung des Landes Nordrhein-Westfalen Kap. 0212 Tit. 68 511.