Stimulation of pepsinogen secretion in permeable isolated gastric glands

1985 ◽  
Vol 249 (3) ◽  
pp. G408-G415
Author(s):  
S. H. Norris ◽  
S. J. Hersey
Keyword(s):  
Lactate Dehydrogenase ◽  
Gastric Glands ◽  
Cholecystokinin Octapeptide ◽  
Chief Cells ◽  
Isolated Gastric Glands ◽  
Pepsinogen Secretion ◽  
Calcium Stimulation ◽  
Intracellular Regulation ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Rabbit isolated gastric glands were treated with digitonin so that stimulation of pepsinogen secretion could be studied in a permeable system. Criteria for permeabilization were the release of lactate dehydrogenase in response to digitonin as well as the finding that calcium stimulation and spermine inhibition required the presence of digitonin. Other evidence confirmed that digitonin directly permeabilized chief cells. Pepsinogen secretion was elicited from digitonin-treated gastric glands by a number of agents, including calcium, vanadate, cholecystokinin octapeptide (CCK-OP), 8-bromo-adenosine 3',5'-cyclic monophosphate, and forskolin. Spermine was found to inhibit secretion stimulated by each of these agents only in the presence of digitonin, suggesting an intracellular site of spermine action. We concluded that spermine inhibition of secretion could be used as a marker of secretion elicited from permeable chief cells. The ability to stimulate pepsinogen secretion by such agents as CCK-OP and forskolin suggests that stimulus-secretion coupling is virtually intact even in permeable chief cells. We felt that this preparation should offer unusual opportunities for investigating the mechanisms involved in the intracellular regulation and activation of pepsinogen secretion.

Stimulation of pepsinogen release from isolated gastric glands by cholecystokininlike peptides

1983 ◽  
Vol 244 (2) ◽  
pp. G192-G197 ◽  
Author(s):  
S. J. Hersey ◽  
D. May ◽  
D. Schyberg
Keyword(s):  
Acid Formation ◽  
Weak Base ◽  
Gastric Glands ◽  
Cholecystokinin Octapeptide ◽  
Peptide Receptor ◽  
Isolated Gastric Glands ◽  
Pepsinogen Secretion ◽  
Weak Stimulus ◽  
Peptide Stimulation ◽  
Stimulation Of

Gastric glands isolated from rabbit stomach were employed to study the regulation of pepsinogen secretion by peptide hormones. Cholecystokinin octapeptide (CCK-OP) stimulated pepsinogen secretion with an ED50 of about 1 nM. Caerulein was as effective as CCK-OP but less potent (ED50, 10 nM). Gastrin (HG-17) was found to be a weak stimulus, being only about 20% as effective as CCK-OP or caerulein. Sulfation of CCK-OP and caerulein was found to be important for potency but did not alter efficacy. Peptide stimulation of pepsinogen secretion was unaffected by cimetidine, atropine, or propranolol. Combinations of peptides resulted in less-than-additive responses, as did the combination of peptides with carbachol. In contrast, combination of peptides with isoproterenol resulted in additive responses. Accumulation of the weak base aminopyrine was used to measure acid formation by the gastric glands. The peptides gastrin, CCK-OP, and caerulein were found to be equally effective in stimulating acid formation. The peptide stimulation of pepsinogen secretion was inhibited by dibutyryl cGMP, whereas stimulation of acid formation was not inhibited by the cyclic nucleotide. The results indicate that gastric glands contain at least two peptide receptors distinguishable by sensitivity to dibutyryl cGMP. The peptide receptor associated with pepsinogen secretion appears to be selective for CCK relative to gastrin.

Lack of interaction between acid and pepsinogen secretion in isolated gastric glands

1983 ◽  
Vol 245 (6) ◽  
pp. G775-G779
Author(s):  
S. J. Hersey ◽  
M. Miller ◽  
D. May ◽  
S. H. Norris
Keyword(s):  
Cyclic Nucleotides ◽  
Acid Formation ◽  
Dibutyryl Camp ◽  
Gastric Glands ◽  
Isolated Gastric Glands ◽  
Pepsinogen Secretion ◽  
Inhibited Acid ◽  
Weak Stimulation ◽  
Stimulation Of

Gastric glands isolated from rabbit stomach were employed to study the relation between acid and pepsinogen secretion. The effects of adenosine and guanosine nucleotides were examined for both secretory processes. cAMP, dibutyryl cAMP (DBcAMP), and 8-bromo-cAMP (8BrcAMP) were found to stimulate both acid and pepsinogen secretion with a potency sequence of 8BrcAMP greater than DBcAMP greater than cAMP. Adenosine, ATP, and AMP were ineffective, indicating that the responses to adenosine cyclic nucleotides do not involve an adenosine receptor. 8BrcGMP was found to produce a weak stimulation of both acid and pepsinogen secretions, while GMP, cGMP, and DBcGMP were ineffective. DBcGMP was found to inhibit competitively the stimulation of pepsinogen secretion by cholecystokinin (CCK)-like peptides. No inhibition was found with cGMP or 8BrcGMP. Stimulation of pepsinogen secretion by carbachol or isoproterenol was not inhibited by DBcGMP nor was the stimulation of acid formation by CCK-like peptides. Thiocyanate inhibited acid formation but did not affect pepsinogen secretion stimulated by 8BrcAMP or carbachol, indicating that stimulation of pepsinogen secretion does not require simultaneous acid formation. Costimulation of acid formation by histamine and pepsinogen secretion by isoproterenol showed no interaction between the two secretory processes. The results are interpreted to suggest that correlations between acid and pepsinogen secretion observed in vivo do not result from direct interactions between parietal and chief cells.

Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated stimulation of pepsinogen secretion

1994 ◽  
Vol 266 (4) ◽  
pp. G613-G623 ◽  
Author(s):  
Y. Kitsukawa ◽  
C. Felley ◽  
D. C. Metz ◽  
R. T. Jensen
Keyword(s):  
Guinea Pig ◽  
Initial Phase ◽  
Time Course ◽  
Initial Increase ◽  
Cholecystokinin Octapeptide ◽  
Chief Cells ◽  
Pepsinogen Secretion ◽  
Inositol 1,4,5 Trisphosphate ◽  
Stimulation Of ◽  
Sustained Increase

The roles of Ca2+ in agonist-induced pepsinogen secretion from guinea pig chief cells remain unclear. We used cholecystokinin octapeptide (CCK-8) or secretin alone or with thapsigargin (TG) to clarify these roles. TG releases Ca2+ from intracellular stores by inhibiting microsomal Ca(2+)-adenosinetriphosphatase (ATPase), thereby depleting intracellular Ca2+ (Cai2+) stores. In most cells TG also causes Ca2+ influx. In the present study, with an extracellular Ca2+ concentration ([Ca2+]o) of 1.5 mM, CCK-8 (0.1 microM) caused a rapid increase in pepsinogen secretion; however, the rate decreased with time. With [Ca2+]o = 0, the initial increase was similar but later secretion was abolished, suggesting that Ca2+ influx was important for sustained secretion. With [Ca2+]o = 1.5 mM, TG (0.1 microM) caused a 2.7-fold sustained increase in in Cai2+ concentration ([Ca2+]i) and a ninefold sustained increase in pepsinogen secretion. With [Ca2+]o = 0, TG caused a transient 66% increase in [Ca2+]i and a 50% increase in pepsinogen secretion. The time course of TG-induced pepsinogen secretion correlated with the time course of TG-induced increases in [Ca2+]i. These data demonstrated that Ca2+ influx itself was a potent stimulant of pepsinogen secretion. We further focused on the roles of increasing [Ca2+]i from Cai2+ stores. With or without extracellular Ca2+ (Cao2+) present, addition of CCK-8 (0.1 microM) 10 min after TG caused no further increase in [Ca2+]i, demonstrating depletion of the inositol 1,4,5-trisphosphate-sensitive pool. The Ca(2+)-mobilizing agent CCK-8 caused no pepsinogen secretion 10 min after TG preincubation, demonstrating that mobilization of Ca2+ from intracellular stores was important in the rapid initial phase stimulation of pepsinogen secretion caused by CCK-8. In contrast, preincubation with TG had no effect on pepsinogen secretion by secretin, an agent that increases adenosine 3',5'-cyclic monophosphate. A 6-min preincubation with TG potentiated the subsequent stimulation of pepsinogen secretion caused by secretin in the presence of Cao2+ where [Ca2+]i remained elevated. However, TG-induced potentiations of secretin-stimulated pepsinogen secretion was abolished once [Ca2+]i had returned to the basal level in the absence of Cao2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Ontogeny of pepsin secretory response to secretagogues in isolated rat gastric glands

1986 ◽  
Vol 250 (2) ◽  
pp. G200-G204 ◽  
Author(s):  
J. Yahav ◽  
P. C. Lee ◽  
E. Lebenthal
Keyword(s):  
Term Neonate ◽  
Ionophore A23187 ◽  
Newborn Rats ◽  
Dibutyryl Camp ◽  
Gastric Glands ◽  
Cholecystokinin Octapeptide ◽  
Rat Pups ◽  
Isolated Gastric Glands ◽  
Old Rats ◽  
Isolated Rat

By use of isolated gastric glands from rats at various ages, we demonstrated that full-term neonate and 1-day-old rats showed no response to cholecystokinin octapeptide (CCK-OP), carbachol, or Ca2+ ionophore. The same glands, however, were responsive to dibutyryl cAMP. A mature response was not found until the pups were 2 days old. Injection of hydrocortisone into newborn rats led to an increase in pepsinogen concentrations in gastric glands and also an increased responsiveness to CCK-OP, carbachol, and Ca2+ ionophore A23187 24 h after administration. Hydrocortisone thus caused precocious maturation of both pepsinogen accumulation and pepsinogen secretory responsiveness of gastric glands in rat pups.

Regulation of pepsinogen release from canine chief cells in primary monolayer culture

1983 ◽  
Vol 245 (5) ◽  
pp. G641-G646 ◽  
Author(s):  
M. J. Sanders ◽  
D. A. Amirian ◽  
A. Ayalon ◽  
A. H. Soll
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Functional Differentiation ◽  
Maximal Response ◽  
Chief Cells ◽  
Epithelial Monolayers ◽  
Pepsinogen Secretion ◽  
Primary Monolayer ◽  
Dose Dependent ◽  
Short Term Culture ◽  
Stimulation Of

To study the regulation of pepsinogen secretion by chief cells, we have developed techniques for the isolation, enrichment, and short-term culture of chief cells from canine stomach. The fundic mucosa was enzyme dispersed and chief cells were enriched to a content of about 70% using an elutriator rotor. After 36 h in culture confluent monolayers formed that were highly enriched in chief cells. Carbachol induced a time-dependent release of pepsinogen into the medium, with about a threefold increase in pepsinogen secretion over controls found after 60 min of incubation. Carbachol stimulation of pepsinogen secretion was dose dependent, with 5 microM producing 50% of the maximal response found at a carbachol concentration of 100 microM. Atropine (100 microM) produced a rightward shift of the dose-response curve, indicating the presence of a muscarinic receptor. Dibutyryl cAMP, 8-bromo-cAMP, and forskolin also markedly stimulated pepsinogen secretion. Secretin and vasoactive intestinal peptide (VIP) stimulated pepsinogen secretion, but the response were of smaller magnitude than found with carbachol or the cAMP analogues. The phosphodiesterase inhibitor isobutylmethylxanthine also caused a small stimulation of pepsinogen secretion but did not enhance the response to secretin or VIP. These findings indicate that epithelial monolayers can spontaneously form from isolated canine chief cells and retain functional differentiation evident by a response to stimulation. Canine chief cells in culture possess muscarinic and secretin receptors and respond to cAMP.

Partial agonism by gastrin for a cholecystokinin receptor mediating pepsinogen secretion

1993 ◽  
Vol 265 (5) ◽  
pp. G865-G872
Author(s):  
L. H. Tang ◽  
M. D. Miller ◽  
J. R. Goldenring ◽  
I. M. Modlin ◽  
S. J. Hersey
Keyword(s):  
Partial Agonist ◽  
Specific Binding ◽  
Receptor Occupancy ◽  
Structural Basis ◽  
Tyrosine Residue ◽  
Gastric Glands ◽  
Cholecystokinin Receptor ◽  
Isolated Gastric Glands ◽  
Pepsinogen Secretion ◽  
Type Receptor

Isolated gastric glands from rabbit were used to characterize the functional cholecystokinin (CCK)-like peptide receptors that mediate pepsinogen secretion. Pepsinogen secretion was stimulated by both CCK octapeptide sulfate (CCK-8) and A-71378, a selective CCK-A-type receptor agonist, with similar mean effective doses (1.0 and 0.8 nM, respectively). Compared with CCK-8, gastrin-17 (G-17-I) showed reduced potency and only partial efficacy for stimulation of pepsinogen secretion while inhibiting the maximal CCK-8-stimulated response. The nonpeptide inhibitors, asperlicin and L-364,718, inhibited pepsinogen secretion with identical pA2 values for antagonism of both CCK and gastrin, indicating that both peptides interact with the same functional receptor. Specific binding of [3H]CCK-8 to isolated chief cell membranes was displaced fully by both CCK and gastrin, indicating full receptor occupancy by both peptides. A novel synthetic peptide analogue, pseudogastrin [(Glu)5-Ala-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2], was used to investigate the structural basis for the lower potency and efficacy of G-17-I. The potency of CCK and gastrin analogues for pepsinogen secretion was found to be dependent on both sulfation of a tyrosine residue and the position of the tyrosine residue relative to the COOH-terminal phenylalanine amide. The efficacy appears to be determined partially by the extended NH2-terminal sequence of G-17-I. The results of the present study are interpreted to show that pepsinogen secretion is mediated by a CCK-A-type receptor and gastrin acts at the same receptor as a partial agonist.

Differential effects of GTP gamma S on acid and pepsinogen secretion by permeable gastric glands

1996 ◽  
Vol 270 (6) ◽  
pp. G962-G968 ◽  
Author(s):  
M. D. Miller ◽  
S. J. Hersey
Keyword(s):  
Acid Secretion ◽  
Parietal Cells ◽  
Tetraacetic Acid ◽  
Alpha Toxin ◽  
Gastric Glands ◽  
Differential Effects ◽  
Pepsinogen Secretion ◽  
Stimulus Secretion Coupling ◽  
Gamma S ◽  
Coupling Mechanisms

Gastric glands isolated from rabbit stomach were permeabilized with Staphylococcus aureus alpha-toxin. Acid secretion by parietal cells, as measured by the accumulation of weak base, was inhibited by incubation with alpha-toxin but could be restored by addition of exogenous ATP (1 mM). The permeable glands were found to retain acid secretory responses to receptor-linked secretagogues, histamine and carbachol, as well as to intracellular mediators, forskolin and 8-bromoadenosine 3',5'-cyclic monophosphate, indicating the presence of intact, functional intracellular coupling mechanisms. Both basal and stimulated acid secretion by the permeable glands were blocked by the Mg2+ chelator, trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA; 5 mM), whereas CDTA had no effect on nonpermeabilized glands. These results are interpreted to show that alpha-toxin permeabilizes parietal cells to moderate sized molecules without causing a loss of critical intracellular components. The acid secretory responses to histamine and carbachol persisted in media containing low ( < 50 nM) levels of free Ca2+ buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (0.5 mM), indicating that changes in bulk Ca2+ are not required for these responses. Inclusion of the nonhydrolyzable analogue of GTP, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 100 microM), resulted in inhibition of spontaneous acid secretion, blocked responses to all agents tested, and inhibited stimulated acid secretion. GTP gamma S had no effect on nonpermeabilized glands. No effects on acid secretion by either permeable or nonpermeable glands were observed with GTP, guanosine diphosphate, or guanosine 5'-O-(2-thiodiphosphate). GTP gamma S had no effect on H+ gradient formation by gastric membrane vesicles, showing that it does not inhibit the gastric H(+)-K(+)-adenosinetriphosphatase directly. These results are interpreted to show that GTP gamma S interacts at a postreceptor site to inhibit or reverse a critical step in stimulus-secretion coupling in parietal cells. In contrast to the effect on parietal cells, GTP gamma S was found to stimulate pepsinogen secretion by alpha-toxin-permeabilized chief cells. The differential effects of GTP gamma S on acid and pepsinogen secretions suggest unique roles for GTP binding proteins in these two secretory processes. The use of alpha-toxin-permeabilized gastric glands should prove useful in defining the stimulus-secretion coupling mechanisms involved in both acid and pepsinogen secretions.

Forskolin stimulation of acid and pepsinogen secretion by gastric glands

1983 ◽  
Vol 755 (2) ◽  
pp. 293-299 ◽  
Author(s):  
S HERSEY ◽  
A OWIRODU ◽  
M MILLER
Keyword(s):  
Gastric Glands ◽  
Pepsinogen Secretion ◽  
Stimulation Of

Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1 and M3 muscarinic receptors

2005 ◽  
Vol 289 (3) ◽  
pp. G521-G529 ◽  
Author(s):  
Guofeng Xie ◽  
Cinthia Drachenberg ◽  
Masahisa Yamada ◽  
Jürgen Wess ◽  
Jean-Pierre Raufman
Keyword(s):  
In Situ Hybridization ◽  
Fold Increase ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Double Knockout ◽  
Gastric Glands ◽  
Cholinergic Agonist ◽  
Chief Cells ◽  
Pepsinogen Secretion

Muscarinic cholinergic mechanisms play a key role in stimulating gastric pepsinogen secretion. Studies using antagonists suggested that the M3 receptor subtype (M3R) plays a prominent role in mediating pepsinogen secretion, but in situ hybridization indicated expression of M1 receptor (M1R) in rat chief cells. We used mice that were deficient in either the M1 (M1R−/−) or M3 (M3R−/−) receptor or that lacked both receptors (M1/3R−/−) to determine the role of M1R and M3R in mediating cholinergic agonist-induced pepsinogen secretion. Pepsinogen secretion from murine gastric glands was determined by adapting methods used for rabbit and rat stomach. In wild-type (WT) mice, maximal concentrations of carbachol and CCK caused a 3.0- and 2.5-fold increase in pepsinogen secretion, respectively. Maximal carbachol-induced secretion from M1R−/− mouse gastric glands was decreased by 25%. In contrast, there was only a slight decrease in carbachol potency and no change in efficacy when comparing M3R−/− with WT glands. To explore the possibility that both M1R and M3R are involved in carbachol-mediated pepsinogen secretion, we examined secretion from glands prepared from M1/3R−/− double-knockout mice. Strikingly, carbachol-induced pepsinogen secretion was nearly abolished in glands from M1/3R−/− mice, whereas CCK-induced secretion was not altered. In situ hybridization for murine M1R and M3R mRNA in gastric mucosa from WT mice revealed abundant signals for both receptor subtypes in the cytoplasm of chief cells. These data clearly indicate that, in gastric chief cells, a mixture of M1 and M3 receptors mediates cholinergic stimulation of pepsinogen secretion and that no other muscarinic receptor subtypes are involved in this activity. The development of a murine secretory model facilitates use of transgenic mice to investigate the regulation of pepsinogen secretion.

Bauhinia candicans stimulation of glucose uptake in isolated gastric glands of normal and diabetic rabbits

Fitoterapia ◽  
2006 ◽  
Vol 77 (4) ◽  
pp. 271-275 ◽  
Author(s):  
O. Fuentes ◽  
J. Alarcón
Keyword(s):  
Glucose Uptake ◽  
Gastric Glands ◽  
Isolated Gastric Glands ◽  
Diabetic Rabbits ◽  
Stimulation Of
Sign in / Sign up

Export Citation Format

Share Document