Biomedical subjects

T Shea-Donohue

Publications and source records attributed to T Shea-Donohue.

36 records · Page 2Linked to original sources

PubMed1997

Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models.

Studies with rodents infected with Trichinella spiralis, Heligmosomoides polygyrus, Nippostronglyus brasiliensis, and Trichuris muris have provided considerable information about immune mechanisms that protect against parasitic gastrointestinal nematodes. Four generalizations can be made: 1. CD4+ T cells are critical for host protection; 2. IL-12 and IFN-gamma inhibit protective immunity; 3. IL-4 can: (a) be required for host protection, (b) limit severity of infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines that are stereotypically produced in response to gastrointestinal nematode infections fail to enhance host protection against some of the parasites that elicit their production. Host protection is redundant at two levels: 1. IL-4 has multiple effects on the immune system and on gut physiology (discussed in this review), more than one of which may protect against a particular parasite; and 2. IL-4 is often only one of multiple stimuli that can induce protection. Hosts may have evolved the ability to recognize features that characterize parasitic gastrointestinal nematodes as a class as triggers for a stereotypic cytokine response, but not the ability to distinguish features of individual parasites as stimuli for more specific protective cytokine responses. As a result, hosts deploy a set of defense mechanisms against these parasites that together control infection by most members of that class, even though a specific defense mechanism may not be required to defend against a particular parasite and may even damage a host infected with that parasite.

Animals↗

PubMed1997

Interleukin-4 modulates cholinergic neural control of mouse small intestinal longitudinal muscle.

Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are spasmogenic, potentially causing parasitic expulsion, we investigated the effect of interleukin-4 on smooth muscle and the mast cell and mediator dependency of this effect. BALB/c, mast cell-deficient W/Wv mice, 5-lipoxygenase-efficient mice, and their littermate controls were injected with interleukin-4-anti-interleukin-4 antibody complexes that chronically increase serum interleukin-4 levels. Mid-small intestinal segments, hung longitudinally in organ baths, were stimulated electrically or by agonists. The cholinergic response to electrical field stimulation was significantly increased by interleukin-4 treatment in BALB/c but not W/Wv mice. The enhanced cholinergic contraction was not due to increased acetylcholine responsiveness but was dependent on leukotriene D4, since it was reversed by leukotriene D4 receptor antagonism, and not observed in 5-lipoxygenase knock-out mice. Leukotriene D4 responsiveness was unaffected by interleukin-4 treatment. We conclude that interleukin-4 amplifies cholinergic excitation through a mast cell and leukotriene D4-dependent mechanism.

Acetylcholine↗

PubMed1997

Role of sensory afferents in the myoelectric response to acute enteric inflammation in the rabbit.

The role of sensory afferents in inflammation-induced alterations in myoelectric activity in vivo was investigated in the rabbit small intestine. Isolated ileal loops were implanted with serosal electrodes and exposed to ricin or vehicle after pretreatment with 125 mg/kg of subcutaneous (125 mg over 3 days) or intraluminal (640 microM) capsaicin. After 5 h of myoelectric recording, the loops were prepared for histology and for ex vivo generation of eicosanoids. Capsaicin exacerbated mucosal damage after exposure to ricin but did not alter neutrophil infiltration. Subcutaneous capsaicin alone elevated slow-wave frequency and spike events and transiently suppressed the myoelectric response to ricin. In contrast, intraluminal capsaicin alone did not alter myoelectric activity but produced a sustained inhibition of the response to ricin. Eicosanoid production was unchanged by capsaicin alone. Intraluminal capsaicin blocked increases in leukotriene C4 and prostaglandin E2 during inflammation, an effect that paralleled its inhibition of myoelectric activity. Thus the contribution of sensory afferents to altered motility during acute ileitis involves the release of mucosal inflammatory mediators that influence neural control of smooth muscle.

Acute Disease↗

PubMed1997

Tachykinergic neurotransmission is enhanced in small intestinal circular muscle in a rabbit model of inflammation.

Previous electrophysiological studies have shown that tachykinin-mediated excitatory junction potentials are enhanced in a ricin model of inflammatory bowel disease. The present study extends these findings by investigating the contractile response to stimulation of noncholinergic nerves and tachykinin agonists. According to rank order potencies, the rabbit ileal circular muscle was neurokinin (NK)1 preferring, and the response to these agonists was down-regulated by acetylcholine and up-regulated by nitric oxide. In ricin-treated tissue, cholinergic and nitridergic modulation was lost; in the presence of atropine and N-nitro-L-arginine methyl ester, or tetrodotoxin, the response to NK1 and NK2 agonists was enhanced. The noncholinergic response to nerve stimulation was predominantly mediated by NK1 receptors, and the enhanced response of ricin-treated tissue to NK1 agonists probably contributes to the increased response to electrical field stimulation observed under these conditions. Increased tachykinin response and loss of control of this response by acetylcholine and nitric oxide are likely to have profound effects on intestinal motility and could contribute to some of the symptomology of inflammatory bowel disease.

Acetylcholine↗

PubMed1996

Local TH1 and TH2 responses to parasitic infection in the intestine: regulation by IFN-gamma and IL-4.

Control of parasitic infections is dependent on the production of cytokines that activate mechanisms which limit invasion, reproduction or survival of the parasite. In contrast, conditions that induce inappropriate cytokine responses facilitate the spread of infection and ultimately exacerbate the level of disease. Measurement of local cytokine responses to different gastrointestinal parasites, such as the intracellular protozoan, Cryptosporidium parvum, and luminal dwelling nematodes like Nippostrongylus brasiliensis and Heligmosomoides polygyrus, reveal stereotype response patterns. In general, intracellular parasites stimulate type 1 responses where IFN-gamma is the predominant immune activator, while extracellular parasites stimulate type 2 responses where IL-4 plays a prominent role in elevating humoral immune mechanisms. Cytokines alter cellular function and the milieu of the intestinal lumen to affect the outcome of an infection. The importance of a particular response during the course of an infection can be studied by selective enhancement with an excess of exogenous recombinant cytokine or cytokine antagonists. For example, exogenous IL-12 enhances resistance to C.parvum, but suppresses the normally rapid cure of an infection with N. brasiliensis. Both mechanisms are dependent on expression of IFN-gamma. At the molecular level, exogenous IL-12 stimulates IFN-gamma production which elevates a protective type 1 response to C. parvum but converts the normally anti-worm type 2 response to a type 1 response that inappropriately regulates the infection. Alternatively, excess IL-4 plays a prominent role in modulating effector elements that change intestinal physiology to create a hostile environment for worm parasites. Exogenous IL-4 can cure chronic worm infection, while IL-4 antagonists interfere with protective responses to infection. These observations provide a paradigm for analysis of stereotype responses to different gastrointestinal parasites, and demonstrate how cytokine-induced immune system-dependent and independent effector mechanisms can limit parasitic infection, while inappropriate cytokine responses can exacerbate the state of disease.

Animals↗

PubMed1996

Diaspirin cross-linked hemoglobin is efficacious in gut resuscitation as measured by a GI tract optode.

The objective of this study was to compare the efficacy of diaspirin cross-linked hemoglobin (DCLHb) with that of standard resuscitative fluids in restoring intestinal mucosal oxygenation and villous architecture after hemorrhage. Male rats were bled to a base deficit of 5 +/- 2 nmol/l under propofol anesthesia and monitored for 90 minutes postresuscitation with DCLHb, blood, lactated Ringer's solution, albumin, or nothing (DNR) for mucosal oxygen tension (Pmo2) and physiologic and laboratory parameters. Small intestinal histologic specimens were obtained and scored independently by two investigators blinded to therapy on a scale of 0 (normal) to 4 (worst). All treatments restored Pmo2; only DCLHb did so without exceeding baseline values. For untreated rats (DNR), Pmo2 was not restored. Normal mucosal architecture was maintained only in DCLHb-treated rats. As Pmo2 increased, mucosal score improved. In a rat model of controlled hemorrhage, Pmo2 changes measured by an optode correlated with gut histological abnormalities. By these criteria, DCLHb is superior to crystalloid, colloid, and blood in gut resuscitation.

Animals↗

PubMed1995

Induction of heat-shock protein 72 protects against ischemia/reperfusion in rat small intestine.

BACKGROUND & AIMS: Induction of heat-shock protein 72 is associated with enhanced tolerance to subsequent nonthermal stresses. This study evaluated whether induction of heat-shock protein 72 protects against intestinal ischemia/reperfusion injury. METHODS: Groups of nonheated and heated rats underwent sham operation, 30 minutes of ischemia by occlusion of the superior mesenteric artery, or ischemia followed by 60 minutes of reperfusion. Whole-body hyperthermia to a core temperature of 41.5-42 degrees C for 15-20 minutes was followed by passive cooling 2-3 hours before the experiment. Samples of small intestine were obtained for determination of heat-shock protein 72 production and ex vivo generation of prostaglandin E2 and leukotriene B4 and for histological assessment of mucosal injury and number of neutrophils. RESULTS: Hyperthermia significantly increased heat-shock protein 72 production and significantly reduced ischemia/reperfusion-induced mucosal injury, neutrophilic infiltration, and leukotriene B4 production. Levels of leukotriene B4 and numbers of neutrophils were well correlated in nonheated (r = 0.72) but not in heated groups (r = -0.16). The elevation of prostaglandin E2 levels in response to ischemia and reperfusion was unaltered by hyperthermia. CONCLUSIONS: The mechanism of heat stress-induced protection against intestinal ischemia/reperfusion injury involves inhibition of leukotriene B4 production and subsequent prevention of neutrophil activation and chemotaxis.

Animals↗

PubMed1995

Changes in enteric neural regulation of smooth muscle in a rabbit model of small intestinal inflammation.

In vitro electrophysiological studies of ileal circular muscle from rabbits with ricin-induced inflammation were performed to investigate whether altered neural control or myogenic activity contributes to previously described changes in in vivo myoelectric activity. Ricin treatment increased mean slow-wave amplitude but not frequency or resting membrane potential. Prolonged electrical field stimulation evoked a hyperpolarization during the stimulus train and a depolarization on cessation of stimulation. In the presence of atropine, the depolarization was larger in ricin-treated tissue than in control tissue, showing that ileitis enhanced noncholinergic excitation. The nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester reduced the hyperpolarization in ricin-treated but not in control tissue, suggesting that inflammation increased nitric oxide-mediated inhibition. Substance P desensitization reduced noncholinergic excitation and mean slow-wave amplitude only in ricin-treated tissue, demonstrating that changes in these parameters during inflammation resulted from increased release of, or sensitivity to, tachykinins. These data suggest that acute ileitis alters tachykinin- and nitric oxide-mediated neurotransmission that may affect the normal pattern of ileal motility and/or sensory reflexes.

Animals↗

PubMed1995

Neural control of mouse small intestinal longitudinal muscle: interactions with inflammatory mediators.

The present study was undertaken to investigate neural control of mouse small intestinal longitudinal muscle. Electrical field stimulation evoked acetylcholine- and neurokinin A-mediated contractile responses, whereas nitric oxide-mediated neurotransmission resulted in relaxation. The inflammatory mediators, histamine and leukotriene D4, contracted the longitudinal muscle preparation. Histamine-evoked contractions resulted from binding to histamine H1 receptors on non-neural cells of the small intestine. Leukotriene D4 played a role in neurokinin A-mediated excitation as the leukotriene D4 receptor antagonist, WY 48,252, reduced the response to nerve stimulation under noncholinergic conditions by almost 80%. In contrast, WY 48,252 had no effect on the response to exogenous neurokinin A, indicating that the response to this neurotransmitter is not mediated by leukotriene D4 release. Subthreshold concentrations of leukotriene D4 did not modify the response to neurokinin A, ruling out a synergistic relationship between these two agonists. Leukotriene D4 did not cause synaptic transmitter release through ganglionic stimulation, because its contractile effect was tetrodotoxin insensitive, and did not contribute to noncholinergic excitation through stimulation of neurokinin A release, as the neurokinin2 receptor antagonist, MEN 10,376, did not alter the response to leukotriene D4. Instead leukotriene D4 may modulate the release of neurokinin A from nerve endings during nerve stimulation.

Amino Acid Sequence↗

PubMed1994

Intestinal myoelectric response in two different models of acute enteric inflammation.

The inflammatory responses to intraluminal administration of the cytotoxic lectin ricin or the hapten 2,4,6-trinitrobenzenesulfonic acid in 25% ethanol were compared. Myoelectric activity was recorded from in vivo ileal loops in rabbits after administration of either agent. At the end of a 6-h study the loops were removed and prepared for histological evaluation and for ex vivo generation of leukotriene (LT) C4 and prostaglandin (PG) E2. Both agents induced significant increases in mucosal damage, polymorphonuclear leukocyte infiltration, and edema. These changes tended to be patchy in the hapten model and confluent in the ricin model. Spike burst activity and mucosal LTC4 and PGE2 generation were also enhanced significantly. Intraluminal administration of the specific LTD4 antagonist Wy-48252 1 h before either inflammagen, significantly inhibited the myoelectric response without affecting tissue morphology or eicosanoid synthesis. These data demonstrate that there is a stereotypic spike burst response to acute inflammation, which is mediated in part by LTD4.

Acute Disease↗

PubMed1992

Effect of leukotriene D4 on gastric emptying and secretion in rhesus monkeys.

Gastric function was evaluated in conscious rhesus monkeys after an i.v. infusion of saline (0.11 ml/min) or leukotriene D4 (LTD4) (0.1 or 0.2 microgram/kg/min), a s.c. injection of nordihydroguaiaretic acid (4,4'-(2,3-dimethyl-1,4-butanediyl)-bis[1,2-benzenediol]) (NDGA), a nonspecific lipoxygenase inhibitor, or an intragastric bolus of (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl] methane sulfonamide) (Wy-48,252), a LTD4 receptor antagonist. Using a technesium diethylenetriamine-pentaacetic acid dilution technique, gastric emptying and secretion were determined in response to an 80-ml load of water. At the end of some studies, the animals were gastroscoped to obtain biopsies for histological evaluation. There were no differences in the microscopic appearance of the mucosa among the various groups. A continuous infusion of LTD4 significantly inhibited hydrogen and sodium ion secretion at doses that had no effect on systemic blood pressure or heart rate. In contrast, NDGA and Wy-48,252 had no effect on unstimulated (basal) fluid or ion secretion. Gastric emptying after the water load was unaltered by LTD4, but high doses of NDGA or Wy-48,252 decreased gastric emptying during the first 10 min. Thus, LTD4 does not appear to play a major role in gastric emptying or secretion in response to a water load, but may contribute to the changes in gastric function in response to potential gastric irritants.

Animals↗

PubMed1992

Effects of a prostacyclin analog, U-68,215, on gastric acid secretion, gastric emptying and systemic blood pressure in primates.

The effect of the prostacyclin analog U-68,215 on gastric function and systemic blood pressure was evaluated in a primate model. Starting 30 min after histalog (1 mg/kg s.c.), gastric acid secretion and gastric emptying were determined over a 30-min period using a 99mTc-diethylene triamine pentaacetic acid dilution technique. Each animal then received an intragastric bolus of 0, 25, 50 or 100 micrograms/kg of U-68,215 and, after a 30-min equilibration period, gastric function was determined for an additional 60 min (histalog + U-68,215). Systemic blood pressure and heart rate were measured periodically using a pressure cuff and a Korotkoff microphone. U-68,215 produced a 94% maximum suppression of acid output from 60 to 90 min after 100 micrograms/kg U-68,215. Gastric emptying was significantly inhibited by all doses of U-68,215, and no diarrhea was observed in response to any dose of U-68,215. Systolic blood pressure was significantly inhibited (P less than .05) only after the 100 micrograms/kg, whereas diastolic blood pressure was reduced significantly (P less than .05) by both 50 and 100 micrograms/kg and was positively correlated with acid secretion (r = .53; P less than .05). These data demonstrate that U-68,215 produces a significant inhibition of acid secretion without the stimulatory effect on gastric emptying induced by PGE analogs. Thus, prostacyclin analogs may represent an attractive alternative to PGE analogs in the treatment of peptic ulcer disease.

Animals↗

PubMed1990

Aspirin-induced changes in gastric function: role of endogenous prostaglandins and mucosal damage.

The relative roles of prostaglandins and mucosal injury in aspirin-induced changes in gastric function were evaluated. Conscious rhesus monkeys received a subcutaneous injection of sodium bicarbonate or aspirin (25, 50, 100, or 150 mg/kg) and sodium bicarbonate or 150 mg/kg aspirin subcutaneously plus oral sucralfate (25 mg/kg twice a day). Gastric emptying and fluid and H+ outputs were determined during a fasting period and after an 80-ml water load using a 99mTc-diethylenetriaminepentaacetic acid dilution technique. At the end of each study, the monkeys were gastroscoped to assess mucosal damage, which was ranked blindly on a scale of 0 to 5. Biopsy samples were taken from antrum and fundus for determination of prostaglandins and histological evaluation. All doses of aspirin significantly suppressed prostaglandins in both the antrum and fundus. In contrast, the aspirin-induced increase in gastric mucosal injury was dose dependent. Aspirin also produced a dose-dependent decrease in gastric emptying that was significantly correlated with erosions scores. When aspirin-induced lesions were prevented by sucralfate, the inhibition of gastric emptying was blocked during the fasting period and was attenuated following the water load. Acid secretion was also decreased significantly by aspirin. This action was not modified by sucralfate protection, suggesting that aspirin has a direct inhibitory effect on parietal cell secretion. These data show that mucosal damage contributes significantly to the aspirin-induced changes in gastric function. Moreover, prostaglandins may play a role in the control of gastric emptying, especially during early phase of the response to a water load.

Animals↗

PubMed1990

Kappa agonists inhibit gastric emptying but not acid secretion in rhesus monkeys.

Gastric function was evaluated in rhesus monkeys during a continuous, s.c. infusion of three kappa agonists; dynorphin-(1-13), (trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methanesulfonate hydrate) (U50,488H) and ketocyclazocine (KETO). A dye dilution technique was used to determine gastric fractional emptying rate, hydrogen ion, sodium ion and fluid secretion after the intragastric administration of a water meal. All agonists significantly inhibited fractional emptying rate after the water meal. The kappa receptor antagonist, (-)-(1R,5R,9R)-5,9-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomor pha n methanesulfonate, prevented the inhibitory response to dynorphin-(1-13) and partially blocked the effect of KETO, but, at the dose used in the present study, was completely ineffective against the specific kappa agonist, U50,488H. This suggests that dynorphin-(1-13) and U50,488H may not bind to the same kappa receptor isotype. The partial antagonism of KETO by both naloxone and (-)-(1R,5R,9R)-5,9-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomor pha n methanesulfonate is consistent with a kappa/mu effect of this compound. Naloxone, at the dose used in these studies, did not modify the response to U50,488H. In contrast to their inhibitory action on gastric emptying, the kappa agonists, dynorphin-(1-13) and U50,488H, did not alter acid secretion. The suppressive action of KETO on acid secretion may be due to activation of mu receptors. The inhibitory effect of dynorphin-(1-13) on sodium output was blocked by (-)-(1R,5R,9R)-5,9-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomor pha n methanesulfonate, suggesting a role for kappa agonists in the control of nonparietal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1988

The role of the capillary wall in restricting diffusion of macromolecules. A study of peritoneal clearance of dextrans.

In 5 nephrectomized rabbits the peritoneal clearance of neutral dextrans from plasma to dialysate decreased from 7.8 to 3.3 microliters/kg/min as molecular mass increased from 17,000 to 43,000 daltons, and was relatively constant at 2.8 microliters/kg/min from 49,000 to 97,000 daltons in accord with prior studies. The clearance from dialysate to plasma was measured by determining the distribution volume, which averaged 72 ml/kg, and the plasma concentration 5 h after intraperitoneal instillation. Inward clearances ranged from 11.4 to 19.9 microliter/kg/min, did not correlate well with solute size and were significantly higher than outward clearances. The data suggest that while the capillary wall is the major barrier to macromolecule transfer, absorption can bypass vascular capillaries and occur via the lymphatics. It is suggested that lymphatic flow rate from the peritoneum exceeds 16 microliter/kg/min.

Animals↗

PubMed1986

Gastric protection by sucralfate. Role of mucus and prostaglandins.

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Alterations in gastric mucus secretion in rhesus monkeys after exposure to ionizing radiation.

The aim of the present study was to evaluate the effect of gamma-irradiation on soluble gastric mucus. Six conscious chair-adapted rhesus monkeys were studied once before and twice after exposure to ionizing irradiation (800 rads). Using a marker (99mTc-DTPA) dilution technique, acidic glycoprotein (AG), neutral glycoprotein (NG), ion, and fluid output were determined during a basal period and after the administration of an 80-ml water load. Irradiation significantly increased the outputs of both AG and NG during the basal period. After the water load, NG output remained elevated but irradiation abolished postload AG output thus inhibiting the normal rise in AG output stimulated by the load. Two days after irradiation NG output had returned to control levels whereas AG output was still suppressed. Sodium and potassium ion outputs were unaltered by irradiation. Chloride and fluid outputs were significantly inhibited on the day of irradiation but had returned to control levels within 3 days. These results indicate that irradiation produces significant changes in both the quantity and nature of the soluble mucus glycoproteins secreted into the gastric juice. It is suggested that these changes may compromise the protective ability of gastric mucus.

Animals↗

PubMed1985

The role of endogenous prostaglandins in the regulation of gastric secretion in rhesus monkeys.

Prostaglandins (PG) are known to alter a variety of gastrointestinal functions, but the physiological role of endogenous PG remains unclear. This experiment was designed to evaluate changes in gastric secretion following both acute and chronic inhibition of PG synthesis with indomethacin (5 mg/kg s.c.). Gastric juice was collected by continuous aspiration in 8 conscious chair-adapted male rhesus monkeys following treatment with saline or indomethacin for one or four days. The gastric juice was analyzed for H+, Na+, K+, and Cl- concentrations. The amount of soluble mucus in the gastric juice was estimated using Alcian Blue dye binding of acidic glycoproteins and Periodic Acid Schiff reaction with neutral glycoproteins. PG levels were measured in the plasma and in biopsy samples of fundus, antrum and duodenum. Both one and four days of indomethacin significantly (p less than 0.05) decreased tissue PG levels in the fundus, antrum and duodenum. Plasma levels of PGF2 alpha were significantly (p less than 0.05) decreased after both one and four days of indomethacin, while PGE2 and 6-keto PGF1 alpha were significantly inhibited only after four days of indomethacin. Both acute and chronic inhibition of PG synthesis was accompanied by a decrease in the concentration of sodium and mucus in the gastric juice but by an increase in the output and concentration of hydrogen ion. These changes suggest a possible mechanism by which endogenous PG play a role in the regulation of gastric secretion and in the protection against gastrointestinal damage.

Animals↗