Prostaglandin E2-histamine in interactions on cAMP, cGMP, and acid production in isolated fundic glands

Relations among cAMP, cGMP, acid production [measured by the intraglandular accumulation of [14C]aminopyrine (AP)], and prostaglandin E2 (PGE2) activity were studied in isolated glands from rabbit fundic mucosa. AP, cAMP, and cGMP responses to histamine, PGE2, and 3-isobutyl-1-methylxanthine (IMX) were compared with controls. Histamine and PGE2 significantly increased glandular cAMP levels twofold, and histamine and IMX stimulated AP uptake two- to fourfold. PGE2 significantly inhibited both histamine- and IMX-stimulated AP accumulation, but it did not alter basal AP uptake. PGE2 also decreased histamine-stimulated cAMP production but only at a low concentration (10(-7) M). This dose of PGE2 was near to the endogenous PGE2 content found in unstimulated glands (10(-8) M). Intraglandular cGMP levels in unstimulated glands (10(-8) M). Intraglandular cGMP levels were increased by IMX but not by PGE2 or histamine. It is concluded that histamine stimulation of acid secretion is mediated by cAMP, that secretory and biochemical responses to histamine are modulated by PGE2 because PGE2 antagonized histamine-stimulated cAMP and AP uptake, and that the rise in cAMP induced solely by PGE2 appears to be localized within nonparietal cells because PGE2 alone did not stimulate AP accumulation.

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Oxygen consumption during cimetidine and prostaglandin E2 inhibition of acid secretion.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1978.234.5.e445 ◽

1978 ◽

Vol 234 (5) ◽

pp. E445

Author(s):

L Y Cheung ◽

F G Moody ◽

K Larson ◽

S F Lowry

Keyword(s):

Oxygen Consumption ◽

Steady State ◽

Prostaglandin E2 ◽

Acid Secretion ◽

Acid Production ◽

Inhibitory Action ◽

O2 Consumption ◽

Greater Curvature

Oxygen consumption was determined during cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion in exteriorized segments of the greater curvature of dog stomach. Steady-state acid secretion during histamine infusion correlated well with O2 consumption (r = 0.85, P less than 0.01). Cimetidine and 16,16-dimethyl prostaglandin E2 inhibition of acid secretion produced a reduction of oxygen consumption to resting levels. In contrast, oxygen consumption did not decrease appreciably during thiocyanate inhibition of acid secretion. These observations suggest that the inhibitory action of cimetidine and 16,16-dimethyl prostaglandin E2 precedes, whereas that of thiocyanate is at a point beyond the transfer of energy to the process of acid production.

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Prostaglandin E2-binding sites and cAMP production in porcine fundic mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.241.4.g313 ◽

1981 ◽

Vol 241 (4) ◽

pp. G313-G320

Author(s):

B. L. Tepperman ◽

B. D. Soper

Keyword(s):

Adenylate Cyclase ◽

Prostaglandin E2 ◽

Binding Site ◽

Binding Sites ◽

Biologically Active ◽

Cyclase Activity ◽

Adenylate Cyclase Activity ◽

Scatchard Analysis ◽

Fundic Mucosa ◽

Stimulation Of

Biologically active [3H]prostaglandin E2 (PGE2) bound rapidly and specifically to membrane fractions from hog fundic mucosa. Optimal binding occurred in the 30,000-g membrane preparation at 37 degrees C (pH 5.0). Scatchard analysis of specific PgE2 binding revealed the presence of a heterogeneous population of binding sites with Kd values and binding site concentrations of approximately 1 X 10(-9) M and 1 fmol/mg prot and 2 X 10(-8) M and 20 fmol/mg prot, respectively. Specific binding was inhibited by the following agents in descending order of potency: PGE1, PGA2, PGD2, 6-keto-PGF1 alpha, and thromboxane B2. Trypsin treatment or boiling reduced or abolished specific PGE2 binding. PGE2 stimulated cAMP formation in the 2,500-g fraction, with an approximate Km of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not b of 1 X 10(-6) M, but stimulation of adenylate cyclase activity by PG was not evident in the 16,000-g or 30,000-g tissue preparations. These results suggest that a specific PGE2-binding site exists in the 16,000-g and 30,000-g fractions of porcine fundic mucosa, although an increase in cAMP-forming capacity could not be localized in these fractions in vitro.

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Mechanism of action of γ-aminobutyric acid on frog melanotrophs

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0140001 ◽

1995 ◽

Vol 14 (1) ◽

pp. 1-12 ◽

Cited By ~ 21

Author(s):

L Desrues ◽

H Vaudry ◽

M Lamacz ◽

M C Tonon

Keyword(s):

Intracellular Calcium ◽

Calcium Concentration ◽

Inhibitory Effect ◽

Aminobutyric Acid ◽

Calcium Stores ◽

Camp Production ◽

Biphasic Effect ◽

Camp Levels ◽

Camp Formation ◽

Stimulation Of

ABSTRACT We have previously demonstrated that γ-aminobutyric acid (GABA) is a potent regulator of secretory and electrical activity in melanotrophs of the frog pituitary. The aim of the present study was to investigate the intracellular events which mediate the response of melanotrophs to GABA. We first observed that GABA (1–100 μm inhibited both basal and forskolin-stimulated cyclic AMP (cAMP) formation. The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 μm) and totally abolished by a 4-h pretreatment with pertussis toxin (01 μg/ml). In contrast, the specific GABAA agonist 3-aminopropane sulphonic acid (3APS) did not affect cAMP production. Both GABA and 3APS (100 μm each) induced a biphasic effect on α-MSH release from perifused frog neurointermediate lobes, i.e. a transient stimulation followed by an inhibition of α-MSH secretion. Administration of forskolin (10 μm) prolonged the stimulatory phase and attenuated the inhibitory phase evoked by GABA and 3APS, indicating that cAMP modulates the response of melanotrophs to GABAA agonists. Ejection of 3APS (1 μm) in the vicinity of cultured melanotrophs caused a massive increase in intracellular calcium concentration ([Ca2+]i). The stimulatory effect of 3APS on [Ca2+]i was abolished when the cells were incubated in a chloride-free medium. The formation of inositol trisphosphate was not affected by 3APS, suggesting that the increase in [Ca2+]i cannot be ascribed to mobilization of intracellular calcium stores. ω-Conotoxin did not alter the secretory response of frog neurointermediate lobes to 3APS, while nifedipine blocked the stimulation of α-MSH secretion induced by 3APS. In conclusion, the present data indicate that, in frog pituitary melanotrophs, (i) the stimulatory phase evoked by GABAA agonists can be accounted for by an influx of calcium through L-type calcium channels, (ii) the inhibitory effect evoked by GABAB agonists can be ascribed to inhibition of adenylate cyclase activity and (iii) cAMP attenuates the inhibitory phase evoked by GABAA agonists. Taken together, these data suggest that activation of GABAB receptors may modulate GABAA receptor function.

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Forskolin perturbs cGMP as well as cAMP levels in human thyroid cells

Acta Endocrinologica ◽

10.1530/acta.0.1070225 ◽

1984 ◽

Vol 107 (2) ◽

pp. 225-229 ◽

Cited By ~ 11

Author(s):

Maria Luisa Brandi ◽

Carlo M. Rotella ◽

Andrea Lopponi ◽

Leonard D. Kohn ◽

Salvatore M. Aloj ◽

...

Keyword(s):

Guanylate Cyclase ◽

Cyclase Activity ◽

Human Thyroid ◽

Thyroid Cell ◽

Camp Production ◽

Thyroid Cells ◽

Guanylate Cyclase Activity ◽

Low Concentrations ◽

Camp Levels ◽

Stimulation Of

Abstract. Forskolin, at 10−11 m, stimulates guanylate cyclase activity in primary human thyroid cell cultures, but does not modify cAMP accumulation. At a 10-fold higher concentration it still stimulates guanylate cyclase activity and becomes an inhibitor of cAMP production. Above 10−9 m, forskolin stimulation of cGMP decreases, while it also becomes a stimulator of cAMP production. There is an additive effect of TSH and forskolin on cAMP production at concentrations of the diterpene which are stimulatory. Concentrations of forskolin which are inhibitory for cAMP, but stimulatory for cGMP, are inhibitory for TSH stimulation of cAMP. The addition of 8-bromo-cGMP duplicates the forskolin effect at low concentrations.

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Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y80-042 ◽

1980 ◽

Vol 58 (3) ◽

pp. 243-248 ◽

Cited By ~ 2

Author(s):

N. Schlageter ◽

R. A. Janis ◽

R. T. Gualtieri ◽

O. Hechter

Keyword(s):

Guanylate Cyclase ◽

Cyclic Nucleotide ◽

Phosphodiesterase Inhibitor ◽

Isometric Tension ◽

Free Solution ◽

Cyclic Monophosphate ◽

Opposing Effects ◽

Camp Levels ◽

Camp And Cgmp ◽

Stimulation Of

The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3′,5′-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3′,5′-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly increased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.

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Stimulation of cAMP production and cyclooxygenase-2 by prostaglandin E2 and selective prostaglandin receptor agonists in murine osteoblastic cells

Bone ◽

10.1016/j.bone.2003.12.007 ◽

2004 ◽

Vol 34 (5) ◽

pp. 827-834 ◽

Cited By ~ 41

Author(s):

Yoko Sakuma ◽

Ziaodong Li ◽

Carol C Pilbeam ◽

Cynthia B Alander ◽

Daichi Chikazu ◽

...

Keyword(s):

Prostaglandin E2 ◽

Cyclooxygenase 2 ◽

Osteoblastic Cells ◽

Camp Production ◽

Receptor Agonists ◽

Prostaglandin Receptor ◽

Stimulation Of

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Prostaglandin E2 and the stimulation of rat gastric acid secretion by dibutyryl cyclic 3′,5′-AMP

European Journal of Pharmacology ◽

10.1016/0014-2999(74)90229-5 ◽

1974 ◽

Vol 26 (2) ◽

pp. 204-211 ◽

Cited By ~ 30

Author(s):

I.Harvey M. Main ◽

Brendan J.R. Whittle

Keyword(s):

Prostaglandin E2 ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Stimulation Of

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Somatostatin inhibition of secretagogue and forskolin-stimulated gastric acid secretion

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.254.4.g531 ◽

1988 ◽

Vol 254 (4) ◽

pp. G531-G537

Author(s):

F. Michelangeli ◽

M. C. Ruiz ◽

C. L. Rodriguez ◽

A. Pelacca

Keyword(s):

Acid Secretion ◽

Histamine Release ◽

Inhibitory Effect ◽

Dependent Manner ◽

Direct Stimulation ◽

Histamine Stimulation ◽

Ussing Chambers ◽

Cyclic Monophosphate ◽

Dose Dependent ◽

Stimulation Of

The action of somatostatin (SS) on acid secretion and histamine release was studied in isolated gastric mucosa of toads mounted in Ussing chambers. SS inhibited H+ secretion and histamine release stimulated by cholinergic and gastrinergic secretagogues. Exogenous histamine stimulation of H+ secretion was blocked noncompetitively by SS in a dose-dependent manner. In mucosae maximally stimulated by histamine or forskolin and cimetidine, acetylcholine (ACh) and tetragastrin (TG) induced a direct stimulation of the oxyntopeptic cell not inhibited by SS. Indomethacin, an inhibitor of prostaglandin synthesis, did not prevent SS inhibition of histamine stimulation. Pretreatment with SS abolished forskolin stimulation of H+ secretion. SS induced a small inhibition of the stimulatory effect of N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. These results suggest that SS inhibits acid secretion stimulated by secretagogues through different mechanisms: 1) inhibition of histamine release by ACh and TG, 2) inhibition of endogenous and exogenous histamine stimulation through a blockade of adenylate cyclase, and 3) an inhibitory effect subsequent to the synthesis of adenosine 3',5'-cyclic monophosphate. The direct activation of the oxyntopeptic cell by ACh and TG does not seem to be affected by somatostatin.

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Omeprazole Inhibits Acetylsalicylic Acid-Modified Histamine Stimulation of Acid Secretion in Rabbit Gastric Glands

Canadian Journal of Gastroenterology ◽

10.1155/1994/937679 ◽

1994 ◽

Vol 8 (1) ◽

pp. 15-20 ◽

Cited By ~ 1

Author(s):

Daniel T Brosseuk ◽

Iain GM Cleator ◽

Andrew J Rae ◽

Gilbert Wankling

Keyword(s):

Acetylsalicylic Acid ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Mucosal Injury ◽

Gastric Glands ◽

Histamine Stimulation ◽

Inhibited Acid ◽

Stimulation Of

The effects of misoprostol and omeprazole on basal-, histamine- and acetylsalicylic acid (ASA)-induced gastric acid secretion by isolated rabbit gastric glands were studied. The authors found that ASA at a concentration of 2.4×10-3 M significantly inhibited acid secretion in the isolated gastric glands to 65% of basal levels, and that ASA at a concentration of 2.4×l0-2 M significantly inhibited the histamine stimulation of acid secretion to 78% of maximal. Misoprostol inhibited acid secretion to 76% of basal acid secretion, while omeprazole inhibited secretion to 58% of basal values. Misoprostol inhibited the ASA-modified histamine stimulation to 82% of maximal stimulation. In contrast, omeprazole was able to inhibit the ASA-modified histamine stimulation to 48% of maximal. This omeprazole inhibition of secretagogue-induced acid production reduced acid secretion to levels below basal secretion, indicating that neither histamine nor ASA (at the concentrations used), alone or in combination, had any stimulatory effect in the presence of omeprazole. Misoprostol is the recommended drug of choice for prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury. In vitro results suggest that omeprazole appears to treat this condition more effectively if gastric acid secretion is a necessary prerequisite for NSAID-induced mucosal injury.

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