Flow Secretion Research Articles

Effect of High-Intensity Intermittent Exercise on Secretory IgA Response and Salivary Flow Rate

Effect of High-Intensity Intermittent Exercise on Secretory IgA Response and Salivary Flow Rate

Modelling transport in the anterior segment of the eye.

To model the kinetics of substances, particularly applied substances, in the anterior segment. A simple computational model was developed to describe portions of the anterior segment. First, a two-dimensional vertical slice through the center of a simplified anterior segment was modeled. This incorporated movement of substances by diffusion and by bulk flow in the anterior segment convectional flow. Second, movement by bulk flow in the secretory inflow and drainage of aqueous humor was included. Lastly, the model was extended to three-dimensional form, enabling it to deal with portions of the anterior segment. The model was applied to a number of situations. First, the anterior chamber was loaded with a substance, and entry of fresh aqueous through the pupil was modeled. To model drug applications, a drug was focally applied to the cornea at the limbus, and the distribution of the drug was followed, including arrival at iris targets. In these situations, model results compared reasonably to published experimental observations and findings. For drug distribution, convectional flow was dominant; however, a good match to experimental findings required that secretory flow and drainage be included. A simple computational model appears to be able to give a reasonable description of anterior segment kinetics. Although the speed of secretory flow is small compared to the speed of convectional flow, it can exert substantial effects near the surface of the anterior chamber.

The early secretory pathway contributes to autophagy in yeast.

Autophagy is a starvation response in eukaryotes by which the cell delivers cytoplasmic components to the vacuole for degradation, and is mediated by a double membrane structure called the autophagosome. We have previously proposed that the specific combination of COPII like components, including Sec24p, is required for autophagy (Ishihara, N. et al. (2001) Mol. Biol. Cell, 12: 3690-3702). The autophagic defect in sec24 deleted mutant cells was, however, suppressed upon the recovery of its secretory flow by the overexpression of its homologue, Sfb2p. We have also reported that the autophagic defect is not observed in sec13 and sec31 mutants, a phenomenon that can be explained by the fact that starvation stress suppresses the secretory defect of these mutants. These observations indicate that the active flow in the early secretory pathway plays an important role in autophagy; that is, autophagy proceeds in the presence, but not in the absence of the early secretory flow. Both autophagy and its closely related cytoplasm to vacuole-targeting (Cvt) pathway occur through a pre-autophagosomal structure (PAS), and since the PAS and the functional Cvt pathway exist in all sec mutants, the early secretory pathway must be involved specifically in autophagy, subsequent to PAS formation.

Characterization of ion and fluid transport in human bronchioles.

The regulation of the volume and composition of airway surface liquid is achieved through epithelial ion transport processes. In humans, these processes have been characterized in proximal but not distal airways. Segments of human bronchioles were dissected from surgically removed lung pieces. The transmural potential difference of microperfused bronchioles was inhibited by luminal exposure to amiloride and increased when exposed to the Cl secretagogues forskolin and ATP in the presence of amiloride. Human bronchiolar epithelial cells were cultured on permeable supports and studied in Ussing chambers. They generated a short circuit current (Isc) that decreased in response to amiloride and increased in response to forskolin and to ATP in the presence of amiloride. In low-Cl Kreb's Ringer bicarbonate, the baseline Isc and amiloride-induced decrease in Isc were not different, whereas the forskolin- and ATP-induced increases in Isc were smaller. Fluid transport measurement in excised bronchioles revealed a basal absorptive flow that was reduced by amiloride, whereas forskolin and ATP combined induced a secretory flow in the presence of amiloride. We conclude that human bronchioles actively absorb Na and fluid in unstimulated conditions and are capable of active Cl and fluid secretion when exposed to forskolin and to ATP.

Two NOD Idd-associated intervals contribute synergistically to the development of autoimmune exocrinopathy (Sjögren's syndrome) on a healthy murine background.

The NOD mouse is genetically predisposed to the development of at least 2 autoimmune diseases, autoimmune diabetes and autoimmune exocrinopathy (AEC). More than 19 chromosomal intervals (referred to as Idd regions) that contribute to diabetes susceptibility in the NOD mouse model have been identified, but only 2 chromosomal intervals (associated with Idd3 and Idd5) have been shown to control sialadenitis. In the present study, we bred the Idd3 and Idd5 chromosomal intervals from NOD mice into non-autoimmune C57BL/6 mice to determine if these intervals recreate a Sjögren's syndrome (SS)-like phenotype. C57BL/6.NODc3 mice carrying Idd3 and C57BL/6.NODc1t mice carrying Idd5 were crossed and intercrossed to generate a C57BL/6.NODc3.NODc1t mouse line homozygous for the Idd3 and Idd5 chromosomal intervals on an otherwise disease-resistant genetic background. C57BL/6.NODc3.NODc1t mice were evaluated for biochemical, pathophysiologic, and immunologic markers characteristic of the SS-like phenotype present in the NOD mouse. C57BL/6.NODc3.NODc1t mice fully manifested the SS-like phenotype of the NOD mouse, including decreased salivary and lacrimal gland secretory flow rates, increased salivary protein content due in part to less fluid, aberrant proteolytic enzyme activity, decline in amylase activity, appearance of autoantibodies to exocrine gland proteins, and glandular lymphocytic focal infiltrates. Loss of secretory function occurred more rapidly in C57BL/6.NODc3.NODc1t mice (by 12 weeks of age) than in NOD mice (by 16 weeks of age). No signs of insulitis or autoimmune (type 1) diabetes were observed in the C57BL/6.NODc3.NODc1t mice. Genes located within the 2 chromosomal intervals Idd3 and Idd5 appear necessary and sufficient for manifestation of AEC. We propose that this murine model of SS-like disease be designated C57BL/6.NOD-Aec1Aec2. Identification of specific genes within the Aec1 and Aec2 genetic regions should help elucidate the mechanism(s) underlying SS-like disease.

SEC14-dependent Secretion inSaccharomyces cerevisiae: NONDEPENDENCE ON SPHINGOLIPID SYNTHESIS-COUPLED DIACYLGLYCEROL PRODUCTION

The SEC14 gene in Saccharomyces cerevisiae encodes a phosphatidylinositol transfer protein required for secretory protein movement from the Golgi. Mutation of SAC1, a gene of unknown function, restores secretory flow in sec14-1(ts) strains. The existing model for the bypass of the sec14-1(ts) defect by sac1-22 involves stimulation of sphingolipid biosynthesis and, in particular, the synthesis of mannosyl-diinositolphosphoryl-ceramide with concomitant increases in Golgi diacylglycerol levels. To test this model, we disrupted IPT1, the mannosyl-diinositolphosphoryl-ceramide synthase of S. cerevisiae. Disruption of the IPT1 gene had no effect on the ability of sac1-22 to bypass sec14-1(ts). Furthermore, sphingolipid analysis of sec14-1(ts) and sec14-1(ts) sac1-22 strains showed that mannosyl-diinositolphosphoryl-ceramide synthesis was not stimulated in the bypass mutant. However, the sec14-1(ts) strain had elevated mannosyl-monoinositolphosphoryl-ceramide levels, and the sec14-1(ts) sac1-22 strain showed an 8-fold increase in phosphatidylinositol 4-phosphate along with a decrease in phosphatidylinositol 4,5-bisphosphate. Cellular diacylglycerol levels, measured by [14C]acetate incorporation, did not differ between the sec14-1(ts) and the sec14-1 sac1-22 bypass strains, although disruption of IPT1 in the bypass strain resulted in reduced levels. These data indicate that phosphatidylinositol 4-phosphate, rather than mannosyl-diinositolphosphoryl-ceramide, accumulates in the sec14-1(ts) sac1-22 bypass strain, and that Golgi diacylglycerol accumulation is not required for bypass of the sec14-1(ts) growth and secretory phenotypes.

Isolation of functional Golgi-derived vesicles with a possible role in retrograde transport.

Secretory proteins enter the Golgi apparatus when transport vesicles fuse with the cis-side and exit in transport vesicles budding from the trans-side. Resident Golgi enzymes that have been transported in the cis-to-trans direction with the secretory flow must be recycled constantly by retrograde transport in the opposite direction. In this study, we describe the functional characterization of Golgi-derived transport vesicles that were isolated from tissue culture cells. We found that under the steady-state conditions of a living cell, a fraction of resident Golgi enzymes was found in vesicles that could be separated from cisternal membranes. These vesicles appeared to be depleted of secretory cargo. They were capable of binding to and fusion with isolated Golgi membranes, and after fusion their enzymatic contents most efficiently processed cargo that had just entered the Golgi apparatus. Those results indicate a possible role for these structures in recycling of Golgi enzymes in the Golgi stack.

Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites.

Microtubule disruption has dramatic effects on the normal centrosomal localization of the Golgi complex, with Golgi elements remaining as competent functional units but undergoing a reversible "fragmentation" and dispersal throughout the cytoplasm. In this study we have analyzed this process using digital fluorescence image processing microscopy combined with biochemical and ultrastructural approaches. After microtubule depolymerization, Golgi membrane components were found to redistribute to a distinct number of peripheral sites that were not randomly distributed, but corresponded to sites of protein exit from the ER. Whereas Golgi enzymes redistributed gradually over several hours to these peripheral sites, ERGIC-53 (a protein which constitutively cycles between the ER and Golgi) redistributed rapidly (within 15 minutes) to these sites after first moving through the ER. Prior to this redistribution, Golgi enzyme processing of proteins exported from the ER was inhibited and only returned to normal levels after Golgi enzymes redistributed to peripheral ER exit sites where Golgi stacks were regenerated. Experiments examining the effects of microtubule disruption on the membrane pathways connecting the ER and Golgi suggested their potential role in the dispersal process. Whereas clustering of peripheral pre-Golgi elements into the centrosomal region failed to occur after microtubule disruption, Golgi-to-ER membrane recycling was only slightly inhibited. Moreover, conditions that impeded Golgi-to-ER recycling completely blocked Golgi fragmentation. Based on these findings we propose that a slow but constitutive flux of Golgi resident proteins through the same ER/Golgi cycling pathways as ERGIC-53 underlies Golgi Dispersal upon microtubule depolymerization. Both ERGIC-53 and Golgi proteins would accumulate at peripheral ER exit sites due to failure of membranes at these sites to cluster into the centrosomal region. Regeneration of Golgi stacks at these peripheral sites would re-establish secretory flow from the ER into the Golgi complex and result in Golgi dispersal.

NADPH-diaphorase-positive ganglion cells of the rat adrenal gland: age- and sex-related changes in their number, size, and distribution.

The rat adrenal gland contains ganglion cells able to synthesize nitric oxide (NO). This messenger molecule controls and modulates adrenal secretory activity and blood flow. The present study analyzed the number, size, and distribution of NO-producing adrenal neurons in adulthood and during postnatal development by means of beta-nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. This method reliably visualizes the enzyme responsible for NO generation. The reactive neurons per adrenal gland were 350-400 in both male and female adult rats. The positive nerve cell bodies were mostly located in the medulla, few being detected within the cortex and the subcapsular region. Dual labeling with anti-microtubule-associated protein 2 antibody, specific for neuronal elements, confirmed this distribution. Anti-microtubule-associated protein 1b antibody identified a subset of NADPH-d-positive neurons, displaying different degrees of maturation according to their position within the adrenal gland. At birth, there were about 220 NADPH-d-labeled neurons per adrenal gland in both sexes. As confirmed by dual immunocytochemical labeling, their great majority was evenly distributed between the cortex and the subcapsular region, the medulla being practically devoid of stained neurons. After birth, the number of adrenal NADPH-d-positive ganglion cells displayed a strong postnatal increase and reached the adult-like distribution after 1-2 months. During the period of increase, there was a transient difference in the numbers of these cells in the two sexes. Thus we present here evidence of plasticity in the number, size, and distribution of NADPH-d-positive adrenal neurons between birth and adulthood; in addition, we describe transient sex-related differences in their number and distribution during the 2nd postnatal week, which are possibly related to the epigenetic action of gonadal hormones during this period.

Peptide-containing nerve fibers in the parathyroid glands of different species.

Several neuropeptides, calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP), vasoactive intestinal polypeptide (VIP), the noradrenergic marker dopamine beta-hydroxylase (DBH) and the general neuroendocrine marker PGP 9.5 were localized by immunocytochemistry in the parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep. The general density of innervation varied markedly among the species. Nerve fibers storing CGRP, NPY, PACAP, SP and VIP were present in all species examined. Galanin-containing fibers occurred in all species except guinea-pig and adrenergic (DBH-containing) fibers in all species except chicken and guinea-pig. Generally, the nerve fibers were distributed around blood vessels, in the parenchyma as single scattered fibers, and often also within the capsule. Coexistence studies were performed in cat and sheep. CGRP and SP invariably coexisted in the same nerve fibers. Further, CGRP partially coexisted with PACAP, NPY was observed in the same nerve fibers as DBH. A small population of NPY-containing fibers also seemed to contain galanin (cat only). VIP and NPY coexisted in a population of nerve fibers in the parenchyma. A population of VIP-containing fibers also seemed to contain PACAP. The results indicate the presence of several neuropeptides in the parathyroid glands. As judged by their distribution patterns they may regulate both secretory activity and blood flow, some of them possibly in a cooperative manner.

Altered jejunal potassium (Rb+) transport in piglet rotavirus enteritis.

To determine the mechanisms of K+ loss in viral diarrhea, K+ fluxes (estimated by tracer Rb+ flows) across piglet jejunum in Ussing chambers were determined. Normal jejunum was characterized by an indomethacin-sensitive short-circuit current and a small K+ secretory flow. Rotavirus-infected gut secreted K+ at high rates, probably resulting from increased prostaglandin generation because secretion was abolished by indomethacin. Tissues pretreated with indomethacin responded to 8-bromoadenosine 3',5'-cyclic monophosphate acid and 16,16-dimethyl-prostaglandin E2 with K+ secretion. The secretory response in rotavirus-infected jejunum was no greater than that in normal tissue. Serosal addition of Ca2+ ionophore A23187 caused K+ secretion in normal but not rotavirus-infected jejunum. To inhibit the basolateral uptake of K+ and reduce the driving force for secretion, ouabain was added to the bath. Ouabain unmasked a K+ absorptive process in normal intestine, which was not seen in rotavirus-infected tissue. K+ absorption was inhibited by 3-(cyanomethyl)-2-methyl-8-(phenyl-methoxy)imidazo (1,2 alpha)pyridine (Sch-28080) and omeprazole. We speculate that the high fecal K+ losses observed in human rotavirus enteritis might be caused by an imbalance between K+ secretion and an impaired apical K+ absorptive mechanism in the crypt-type epithelium.

Adenosine and cholinergic-induced gastric contraction in rats.

Adenosine is known for its modulatory effects on gastric secretory function and mucosal blood flow in rats. However, its action on gastric motility has not been defined. The influence of adenosine on gastric contractions provoked by cholinergic drugs and direct vagal stimulation have, therefore, been examined. Bethanechol (25, 50 or 100 micrograms/kg i.v.) and electrical vagal stimulation dose and voltage dependently increased the number and the amplitude of gastric contractions. An adenosine-A1-receptor agonist, L-phenylisopropyladenosine (10 or 50 micrograms/kg s.c.), given 30 min beforehand, did not affect the changes in gastric parameters but decreased the basal mean blood pressure and lessened the reduction in blood pressure evoked by bethanechol. The adenosine-A2-receptor agonist N-ethylcarboxaminoadenosine (1 or 5 micrograms/kg s.c.), 30 min beforehand, however, significantly increased the number but not the force of gastric contractions; a lower dose of this drug increased the basal blood pressure and potentiated the depressive action of bethanechol on systemic blood pressure. Adenosine administration (7.5 mg/kg s.c.) significantly increased its plasma levels at 30 and 60 min after injection; pretreatment with it (2.5, 7.5 or 12.5 mg/kg s.c.), 30 min beforehand, did not affect the gastric and vascular actions of bethanechol. The highest dose of adenosine potentiated the contractile response of vagal stimulation. In the isolated fundus preparation, adenosine added to the organ bath (10(-6), 10(-4), 10(-2) M) also did not affect the contractions induced by acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenum‐preserving resection of the head of the pancreas in chronic pancreatitis with inflammatory mass in the head

In 141 patients with chronic pancreatitis and an inflammatory enlargement of the head of the pancreas, a duodenum-preserving resection of the head of the pancreas was performed within a 16-year period. The hospital mortality was 0.7%; the late mortality was 5%. Seventy-seven percent of the patients were completely free of abdominal pain; 67% returned to their former occupation. After a follow-up period of 3.6 years, glucose metabolism was unchanged in 81.7% of the patients, in 10.1% it deteriorated, and in 8.3% it improved permanently. In patients with severe chronic pancreatitis and an inflammatory mass in the head of the pancreas, a duodenum-preserving resection of the head of the pancreas is an alternative procedure to the Whipple operation. The surgical technique of the duodenum-preserving resection includes 2 major steps: first, subtotal resection of the head of the pancreas conserving the duodenum; second, restitution of the exocrine pancreatic secretory flow from the body and tail of the pancreas by using the first jejunal loop as an interposition. In comparison to the Whipple procedure, the duodenum-preserving resection of the head of the pancreas in chronic pancreatitis spares the patient a gastric resection, a duodenectomy, and a common bile duct resection. With respect to long-lasting pain relief and preservation of the endocrine function of the pancreas, duodenum-preserving resection of the head is a highly effective surgical procedure with a low early and late morbidity and mortality due to the limited surgical resection.

Up-regulation of receptors for IgA on activated human B lymphocytes.

Expression of receptors for the Fc part of IgA (Fc alpha R) by T lymphocytes was recently shown to be up-regulated after activation by T cell mitogens in the absence of IgA. We describe a similar increase on activated human B lymphocytes. Fc alpha R were determined by labelling with human secretory IgA (0.5 mg/ml) and flow cytometry analysis after staining with fluoresceinated goat anti-IgA or goat anti-secretory component F(ab')2 fragments. B-enriched cell suspensions were prepared from peripheral blood or tonsils and activated by Staphylococcus aureus Cowan I, anti-IgM antibodies or E. coli lipopolysaccharide. All three activators increased the percentage of Fc alpha R positive cells although only the former induced significant DNA synthesis. Finally recombinant interleukin 1 (10 nM) and interleukin 2 (10 IU/ml) but not interleukin 4 (300 units/ml) nor low-molecular-weight B cell growth factor induced an increase of Fc alpha R expression. The data show that Fc alpha R can be up-regulated on human B cells in the absence of exposure to IgA.

Blockade and recovery of cholinergic transmission in rats treated with hemicholinium 3

Nerve-induced responses of parotid gland and gastrocnemius muscle were reduced by HC-3 (1 mg kg −1) in proportion to the number of stimuli. Contractions by somatic muscle at 100 Hz were abolished after 6.0 × 10 3 stimuli while 14 × 10 3 were applied at 20 Hz before secretion was blocked. As stimulus rate was decreased, blockade of secretion resulted from fewer stimuli but no difference in ACh content was found between stimulated and unstimulated glands. When stimuli were withheld for 1.5 h transmission recovered temporarily; initial secretory flow rate was only 50% of that in untreated controls when stimulation resumed. In both organs, the time during which responses were sustained, however, was much shorter than when the preparations were stimulated initially. After choline, recovery of transmission was dose-dependent: 150 mg kg −1 were required to restore responsiveness to the muscle and the gland comparable to that in HC-3-treated rats stimulated for the first time. Resting recovery, when stimuli are withheld, probably depends upon stored transmitter becoming mobilized rather than on de novo transmitter synthesis because the endogenous choline in plasma is only 1/1000 of that following exegenous choline.

Transcellular and Paracellular Flow of Water During Secretion in the Upper Segment of the Malpighian Tubule of Rhodnius Prolixus: Solvent Drag of Molecules of Graded Size

ABSTRACT The following molecules graded in size were added to the fluid bathing the blind end of the upper segment of the Malpighian tubules of Rhodnius: urea (U), erythritol (E), mannitol (M), L-glucose (G), sucrose (S), polyethyleneglycol 800 (PEG), raffinose (R), inulin (I) and dextran 15 000–18 000 (D). U, E, M and G distribute themselves within the cell and the extracellular space, while S, PEG, R, I and D are exclusively extracellular. In addition, the net secretory flow of these probes was studied as a function of the net secretory volume flow (Jv). , is made up of a diffusive component , mainly due to unstirred layer effects, and of a convective component , due to the drag (entrainment) of the probes by the water flow. The relative contribution of and of for each probe was studied as a function of Jv. It was found that for U, E, M, G, S and PEG. Therefore these probes are dragged by water. On the other hand for R, I and D, which are not entrained. It is concluded that water flows via extracellular pathways since S and PEG, which are true extracellular probes, are entrained by solvent. In addition to extracellular pathways, it is suggested that the transcellular structures described by Wessing (1965) and Bergeron et al. (1985) could also be the sites of solute-solvent coupling.

Transepithelial transport of nonelectrolytes in the rabbit mandibular salivary gland.

The characteristics of nonelectrolyte secretion by the rabbit mandibular salivary gland have been investigated in an in vitro, perfused preparation. The concentrations of 14C-labeled nonelectrolytes were measured in saliva samples collected over a range of flow rates during the secretory response of the gland to continuous acetylcholine infusion. Of the nine nonelectrolytes studied, the two particularly lipid-soluble molecules, ethanol and antipyrine, appeared in the saliva at approximately the same concentration as in the perfusate, regardless of the secretory flow rate. The more polar molecules (urea, ethanediol, thiourea, glycerol, erythritol, mannitol and sucrose) appeared at saliva/perfusate concentration ratios (phi) which showed a strong dependence on flow. With the exception of thiourea, this could be attributed to the combined contributions of diffusion and solvent drag. For the polar nonelectrolytes, estimates have been obtained of both the permeability coefficients of the gland (P) and the solvent-drag filtration coefficients (1 - sigma). The relation between 1 - sigma and molecular radius suggests that small polar nonelectrolytes and the bulk of the secreted water cross the epithelium via aqueous channels that are approximately 0.8 nm in width. The location of the channels remains uncertain because tissue space measurements indicate that the nonelectrolytes most affected by solvent drag have access to both transcellular and paracellular pathways.

Submandibular salivary secretion in the cat and associated potassium movements: dependence on temperature and perfusate flow rate.

Cat submandibular glands were perfused with Locke solution in a thermostated chamber and intermittently stimulated with 10(-5)M acetylcholine (ACh). In one series of experiments the perfusion pressure was varied within the range 90-60 mm Hg, and secretory flow rate, active K+-reuptake, passive K+-release, and resting and ACh-induced venous flow rates were measured. The ACh-induced secretory flow rate and the maximal K+-fluxes were related to the simultaneous ACh-induced venous flow rates. A proportionality was found between the maximal rate of ACh-induced K+-release and ACh-induced venous flow rates below 8 ml/min, while at higher flow rates the K+-release leveled off. The maximal rate of the post-stimulatory K+-reuptake increased proportionally to the ACh-induced perfusate flow rate throughout the range studied. The secretory flow rate was much less affected by changes in ACh-induced perfusate flow rate. In another series of experiments the gland temperature was varied within the range 12-37 degrees C, and the same parameters were measured. All parameters decreased with cooling being reduced to 50% of their 37 degrees C values at: 24 degrees C for secretion, 19 degrees C for K+-reuptake, and 14 degrees C for K+-release. It is concluded: that the rate of ACh-induced K+-release is limited by the ACh-induced perfusate flow rate (within the physiological range), the capacity of the K+-reuptake mechanism is at least one order of magnitude larger than the maximal rate of K+-reuptake in vivo, the marked temperature sensitivity of the secretory flow rate reflects the high complexity of the mechanisms involved.

Control of potassium transport by turtle colon: role of membrane potential.

To more clearly define the role of the transepithelial electrical potential difference (V m----s), potassium permeability, and sodium-potassium pump rate in transcellular potassium transport by isolated turtle colon, we measured transmural potassium fluxes under open-circuit conditions in the presence and absence of putative blockers of potassium transport: amiloride and barium. The results were consistent with the notion that V m----s is a major determinant of cellular potassium secretion, whereas active potassium absorption is insensitive to changes in V m----s. These observations suggest that "coupling" between colonic sodium absorption and potassium secretion in vivo could be due primarily to the effect of the lumen negative V m----s on transcellular secretory potassium flow. Amiloride-induced inhibition of potassium secretion appeared to be due to the reductions in V m----s and sodium-potassium pump rate that accompanied the inhibition of active sodium absorption.

Canine gastric mucosal vasodilation with prostaglandins and histamine analogs.

The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.