scholarly journals Cholinergically stimulated gastric acid secretion is mediated by M3 and M5 but not M1 muscarinic acetylcholine receptors in mice

2005 ◽  
Vol 288 (6) ◽  
pp. G1199-G1207 ◽  
Author(s):  
Takeshi Aihara ◽  
Yusuke Nakamura ◽  
Makoto M. Taketo ◽  
Minoru Matsui ◽  
Susumu Okabe
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Receptor Subtype ◽  
Gastric Fistula ◽  
Antral Mucosa ◽  
Dependent Manner ◽  
Muscarinic Acetylcholine

Muscarinic acetylcholine receptors play an important role in the regulation of gastric acid secretion stimulated by acetylcholine; nonetheless, the precise role of each receptor subtype (M1–M5) remains unclear. This study examined the involvement of M1, M3, and M5 receptors in cholinergic regulation of acid secretion using muscarinic receptor knockout (KO) mice. Gastric acid secretion was measured in both mice subjected to acute gastric fistula production under urethane anesthesia and conscious mice that had previously undergone pylorus ligation. M3 KO mice exhibited impaired gastric acid secretion in response to carbachol. Unexpectedly, M1 KO mice exhibited normal intragastric pH, serum gastrin and mucosal histamine levels, and gastric acid secretion stimulatied by carbachol, histamine, and gastrin. Pirenzepine, known as an M1-receptor antagonist, inhibited carbachol-stimulated gastric acid secretion in a dose-dependent manner in M1 KO mice as well as in wild-type (WT) mice, suggesting that the inhibitory effect of pirenzepine on gastric acid secretion is independent of M1-receptor antagonism. Notably, M5 KO mice exhibited both significantly lower carbachol-stimulated gastric acid secretion and histamine-secretory responses to carbachol compared with WT mice. RT-PCR analysis revealed M5-mRNA expression in the stomach, but not in either the fundic or antral mucosa. Consequently, cholinergic stimulation of gastric acid secretion is clearly mediated by M3 (on parietal cells) and M5 receptors (conceivably in the submucosal plexus), but not M1 receptors.

Inhibition of gastric acid secretion by oxyntomodulin and its 19-37 fragment in the conscious rat

1993 ◽  
Vol 264 (5) ◽  
pp. G816-G823 ◽  
Author(s):  
C. Jarrousse ◽  
C. Carles-Bonnet ◽  
H. Niel ◽  
R. Sabatier ◽  
M. P. Audousset-Puech ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Gastric Fistula ◽  
Metabolic Clearance ◽  
Target Tissue ◽  
Dependent Manner ◽  
Conscious Rat ◽  
Basal Acid ◽  
Dose Dependent

Oxyntomodulin (Oxm) is a hormone, released from the intestine during digestion. Its target tissue is the gastric mucosa, where it inhibits acid secretion. It contains the 29-amino acid glucagon moiety, extended at its COOH-terminal end by an octapeptide. The glucagon moiety contains a basic doublet (Arg17-Arg18). Our working hypothesis was that the mode of action of Oxm may imply a processing of the molecule at the Arg-Arg doublet, releasing Oxm-(19-37). We compared the effect of Oxm with that of Oxm-(19-37) on gastric acid secretion in the conscious rat provided with a chronic gastric fistula. The acid secretion was plateau stimulated by a perfusion of either pentagastrin or histamine. Whereas Oxm or Oxm-(19-37) had no effect on basal acid secretion, both peptides inhibited pentagastrin (0.5 micrograms.kg-1.h-1)- and histamine (0.4 mg.kg-1.h-1)-stimulated acid secretion in a dose-dependent manner. When the metabolic clearance rate for each peptide was taken into account, the 19-37 fragment was as potent as the whole Oxm, regardless of the type of stimulant. When the dose of pentagastrin was increased from 0.175 to 1.1 micrograms.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) also increased. In contrast, when the dose of histamine was increased from 0.25 to 1.2 mg.kg-1.h-1, the extent of inhibition induced by Oxm (40 pmol/kg) decreased. Oxm-(19-37) (70-140 pmol/kg) displayed the same behavior as the whole molecule under both types of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effects of beta-adrenergic agonists on gastric acid secretion in dogs

1986 ◽  
Vol 251 (4) ◽  
pp. G453-G459
Author(s):  
M. H. Stevens ◽  
R. C. Thirlby ◽  
C. T. Richardson ◽  
M. A. Fredrickson ◽  
R. H. Unger ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Intravenous Infusion ◽  
Acid Output ◽  
Gastric Fistula ◽  
Adrenergic Agonists ◽  
Inhibitory Effects ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists

We evaluated the effect of two beta-adrenergic agonists, isoproterenol (nonselective agonist) and terbutaline (selective beta 2-agonist), on gastric acid secretion stimulated by intravenous pentagastrin, bethanechol, or histamine in dogs with gastric fistulas. Intravenous infusion of isoproterenol or terbutaline inhibited pentagastrin-stimulated acid secretion to a significantly greater extent than they inhibited bethanechol- or histamine-stimulated acid secretion. For example, isoproterenol (12 micrograms X kg-1 X h-1) reduced mean pentagastrin-, bethanechol-, and histamine-stimulated acid output by 86, 63, and 14%, respectively. Percent inhibition of acid secretion with terbutaline (30 micrograms X kg-1 X h-1) averaged 60, 17, and 24% for pentagastrin, bethanechol, and histamine, respectively. Terbutaline also inhibited pentagastrin-stimulated acid secretion from vagally denervated fundic pouches in a dose-related manner. Plasma somatostatin-like immunoreactivity was significantly higher during infusion of terbutaline plus pentagastrin than during infusion of pentagastrin alone. However, an intravenous infusion of 0.3 microgram X kg-1 X h-1 somatostatin-14 had no effect on pentagastrin-stimulated acid secretion from the gastric fistula, even though this infusion increased plasma somatostatin-like immunoreactivity to the same extent as terbutaline plus pentagastrin infusion. Thus the amount of somatostatin released during terbutaline infusion was not sufficient to explain the inhibition of pentagastrin-stimulated acid secretion observed.

Partial purification of a novel stimulant of gastric acid secretion from canine non-antral mucosa

Life Sciences ◽  
1986 ◽  
Vol 38 (10) ◽  
pp. 887-894 ◽  
Author(s):  
N.W. Bunnett ◽  
M.S. Orloff ◽  
Y. Coto ◽  
H.J. Corbet ◽  
R. Garcia ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Partial Purification ◽  
Antral Mucosa

High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice

1998 ◽  
Vol 114 (6) ◽  
pp. 1125-1132 ◽  
Author(s):  
Vicente Martinez ◽  
Annette P. Curi ◽  
Behrooz Torkian ◽  
James M. Schaeffer ◽  
Hilary A. Wilkinson ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Knockout Mice ◽  
Somatostatin Receptor ◽  
Receptor Subtype ◽  
Somatostatin Receptor Subtype 2

Recent advances in the physiology of gastrin

1968 ◽  
Vol 170 (1018) ◽  
pp. 81-88 ◽  
Keyword(s):  
Gastric Secretion ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Chemical Mechanism ◽  
Antral Mucosa ◽  
Aqueous Extracts ◽  
Gastric Digestion ◽  
Hormonal Mechanism ◽  
Vagal Reflex

On 18 May 1905 there was presented at a meeting of this Society a paper in the name of John Sydney Edkins entitled ‘On the chemical mechanism of gastric secretion’ (Edkins 1905). It described experiments in which simple aqueous extracts of antral and fundic mucosa were tested for their power to stimulate gastric secretion when injected as single intravenous doses into anaesthetized cats. Antral extracts excited a secretion of acid and pepsin; fundic extracts did not. Edkins concluded that certain cells in the antral mucosa contained a principle which he named ‘gastrin’; this, he considered, entered the circulation during gastric digestion and stimulated the fundic glands to further activity following on the initial vagal reflex excited by the eating of the meal. These experiments, later recounted in detail (Edkins 1906) initiated more than 40 years of controversy as to the existence of a gastric antral hormone. When attempts were made to confirm and extend Edkins’s observations it was soon discovered that a stimulant of gastric acid secretion could be found not only in antral mucosa but also in many other tissues; and when eventually this ubiquitous agent was identified as histamine (Barger & Dale 1910; Dale & Laidlaw 1910; Popielski 1919) it was widely concluded that the activity of Edkins’s antral extract was due to the presence in it of this substance. The situation was further confused by the failure of apparently well-designed attempts to prove by physio­logical experiment that an antral hormonal mechanism existed, whatever the nature of the hormone. For example, Ivy & Whitlow (1922) and Priestley & Mann (1932) provided dogs with fundic and antral pouches and irrigated the latter with solutions regarded at the time as likely to cause a release of the hormone; but no response from the fundic pouch could be detected, and many years elapsed before the probable reason for such failure became appreciated.

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.

TRH in dorsal vagal complex mediates acid response to excitation of raphe pallidus neurons in rats

1993 ◽  
Vol 265 (5) ◽  
pp. G880-G886 ◽  
Author(s):  
H. Yang ◽  
G. Ohning ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Kainic Acid ◽  
Gastric Fistula ◽  
Dorsal Vagal Complex ◽  
Gastric Function ◽  
Physiological Relevance ◽  
Raphe Pallidus

The role of thyrotropin-releasing hormone (TRH) in the dorsal vagal complex (DVC) in the acid response to excitation of raphe pallidus neurons was investigated in urethan-anesthetized rats with gastric fistula. Kainic acid (0.19 microgram/30 nl) microinjected into the raphe pallidus stimulated gastric acid secretion. The response was prevented by vagotomy. A specific polyclonal TRH antibody, 8964, was raised and characterized (50% inhibitory dose for TRH was 80 pg/ml at an antibody final dilution of 1:10(5)). The TRH antibody injected intracisternally blocked the acid response to intracisternal TRH, but not that of the TRH analogue RX-77368. The TRH antibody (0.33, 0.65, or 1.3 micrograms.100 nl-1.site-1) microinjected bilaterally into the DVC prevented dose dependently by 31, 60, and 76%, respectively, the increase in acid secretion induced by kainic acid injected into the raphe pallidus. The TRH antibody (1.3 microgram/site) microinjected into medullary sites outside of the DVC had no effect. These data indicate that excitation of raphe pallidus neurons induces a vagal-dependent stimulation of gastric acid secretion that is mediated by endogenous TRH in the DVC. TRH neurons in the raphe pallidus projecting to the DVC may have a physiological relevance in the vagal regulation of gastric function.

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