Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat

2005 ◽  
Vol 289 (1) ◽  
pp. G64-G69 ◽  
Author(s):  
Shinichi Kato ◽  
Eitaro Aihara ◽  
Katsuhide Yoshii ◽  
Koji Takeuchi
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Ep Receptor ◽  
Dual Action ◽  
Secretion Inhibition

We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE2 suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE2 was mimicked by sulprostone (EP1/EP3 agonist) but not butaprost (EP2 agonist) or AE1–329 (EP4 agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP1 antagonist), was more potent against pentagastrin- (50% inhibition dose: 3.6 μg/kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 μg/kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1–329 (EP4 agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1–329 was totally abolished by cimetidine as well as AE3–208 (EP4 antagonist). These results suggest that PGE2 has a dual effect on acid secretion: inhibition mediated by EP3 receptors and stimulation through EP4 receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.

Stimulation of neurons in rat ARC inhibits gastric acid secretion via hypothalamic CRF1/2- and NPY-Y1 receptors

2003 ◽  
Vol 285 (6) ◽  
pp. G1075-G1083 ◽  
Author(s):  
Johannes J. Tebbe ◽  
Silke Mronga ◽  
Martin K.-H. Schäfer ◽  
Jens Rüter ◽  
Peter Kobelt ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Receptor Antagonist ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Excitatory Amino Acid ◽  
Inhibitory Effect ◽  
Receptor Subtypes ◽  
Npy Receptor ◽  
Y1 Receptors ◽  
Open Question

Neuropeptide Y (NPY) neuronal projections from the arcuate nucleus (ARC) have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (PVN) as part of the ARC-PVN axis. The existence of a positive feedback loop involving CRF receptors in the PVN has been suggested. Exogenous NPY and CRF in the PVN have been shown to inhibit gastric acid secretion. Recently, we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via vagal pathways. To what extent NPY- and CRF-mediated mechanisms in the PVN contribute to the CNS modulation of gastric acid secretion is still an open question. In the present study, we performed consecutive bilateral microinjections of antagonists to NPY receptor subtypes Y1 and Y2 and to CRF1/2 receptors in the PVN and of the excitatory amino acid kainate in the ARC to assess the role of NPY- and CRF-mediated mechanisms in the kainate-induced effects on gastric acid secretion. Gastric acid secretion was measured at the basal condition and during pentagastrin (16 μg/kg body wt) stimulation. Microinjection of vehicle in the PVN and kainate in the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1 receptor antagonist BIBP-3226 (200 pmol) and the nonspecific CRF1/2 antagonist astressin (30 pmol) in the PVN abolished the inhibitory effect of neuronal activation in the ARC by kainate on gastric acid secretion. The CRF antagonist astressin was more effective. Pretreatment with the NPY-Y2 receptor antagonist BIIE-0246 (120 pmol) in the PVN had no significant effect. Our results indicate that activation of neurons in the ARC inhibits gastric acid secretion via CRF1/2 and NPY-Y1 receptor-mediated pathways in the PVN.

Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

1981 ◽  
Vol 240 (3) ◽  
pp. E274-E278
Author(s):  
Y. Goto ◽  
M. Berelowitz ◽  
L. A. Frohman
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Rat Stomach ◽  
Beta Adrenergic ◽  
Somatostatin Secretion ◽  
Adrenergic Mechanism ◽  
Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

Neuromedin U acts in the central nervous system to inhibit gastric acid secretion via CRH system

2003 ◽  
Vol 284 (6) ◽  
pp. G963-G969 ◽  
Author(s):  
Muhtashan S. Mondal ◽  
Yukari Date ◽  
Noboru Murakami ◽  
Koji Toshinai ◽  
Takuya Shimbara ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Stress Responses ◽  
Energy Homeostasis ◽  
Acid Output ◽  
Inhibitory Effect ◽  
Acid Inhibition ◽  
Dependent Manner ◽  
The Central Nervous System

Neuromedin U (NMU) is a hypothalamic peptide involved in energy homeostasis and stress responses. NMU, when administered intracerebroventricularly, decreases food intake and body weight while increasing body temperature and heat production. In addition, NMU, acting via the corticotropin-releasing hormone (CRH) system, induces gross locomotor activity and stress responses. We studied the effect of intracerebroventricularly administered NMU (0.5–4 nmol) in the regulation of gastric functions in conscious rats. Intracerebroventricular administration of NMU significantly decreased gastric acid output to 30–60% and gastric emptying to 35–70% in a dose-dependent manner. Vagotomy did not abolish the inhibitory effect of NMU on pentagastrin-induced gastric acid secretion. Pretreatment with indomethacin (10 mg/kg), an inhibitor of prostaglandin synthesis, also did not affect NMU-induced acid inhibition. Pretreatment with anti-CRH IgG (1 μg/rat), however, completely blocked NMU-induced acid inhibition ( P < 0.01). Administration of yohimbine (4 mg/kg), an α2-adrenergic receptor antagonist, also abolished NMU-induced acid inhibition ( P < 0.01). These findings suggest that NMU is critical in the central regulation of gastric acid secretion via CRH.

Cholecystokinin inhibits gastric acid secretion through type "A" cholecystokinin receptors and somatostatin in rats

1992 ◽  
Vol 263 (3) ◽  
pp. G287-G292 ◽  
Author(s):  
K. C. Lloyd ◽  
H. E. Raybould ◽  
J. H. Walsh
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Type A ◽  
Inhibitory Effect ◽  
Cck Receptors ◽  
Cholecystokinin Receptors ◽  
Maximum Inhibition ◽  
Vagal Reflex ◽  
Dependent Pathway

The purpose of this study was to determine whether selective antagonism of type "A" cholecystokinin (CCK) receptors blocks inhibition of gastric acid secretion produced by CCK and whether this inhibition is mediated through either a somatostatin-dependent pathway or a vago-vagal reflex. Intravenous infusion of CCK (0.04-10 nmol.kg-1.h-1) dose dependently inhibited pentagastrin-stimulated gastric acid secretion in urethan-anesthetized rats, with a 50% inhibitory dose of 0.9 nmol.kg-1.h-1 and a maximum inhibition of approximately 50%. Blockade of type A CCK receptors using the selective type A receptor antagonist MK-329 completely reversed the inhibitory effect produced by a maximal dose (4 nmol.kg-1.h-1) of CCK. Immunoneutralization of endogenous somatostatin by administration of somatostatin monoclonal antibody abolished the inhibition produced by CCK. Concentrations of somatostatin in portal venous plasma were significantly increased after CCK administration; the increase in somatostatin was blocked by pretreatment with MK-329. In contrast, CCK-induced inhibition of gastric acid secretion was unaltered after perivagal capsaicin treatment. These results indicate that CCK inhibits gastric acid secretion in rats by activation of type A CCK receptors and through release of endogenous somatostatin.

Inhibitory effect of neurotensin on gastric acid secretion in rats

1990 ◽  
Vol 35 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Robert A. Hammer ◽  
Richard E. Hernandez ◽  
Ann Shepard
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect
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