Modulation of murine peritoneal macrophage functions by gastrin

doi:10.1016/0196-9781(95)02133-7

Peptides

Volume 17, Issue 2, 1996, Pages 219-224

https://doi.org/10.1016/0196-9781(95)02133-7 Get rights and content

Abstract

The effect in vitro of gastrin-17 and gastrin-34 was studied at concentrations from 10⁻¹² to 10⁻⁶ M on several functions of resting peritoneal macrophages from BALB/c mice: adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis), and ingestion of inert particles (latex beads) or cells (Candida albicans). Both gastrins, at concentrations from 10⁻¹⁰ to 10⁻⁸ M, inhibited significantly all functions studied with the exception of adherence, which was increased. A dose-response relationship was observed, with a maximum inhibition of macrophage functions found at 10⁻⁹ M. These peptides induced in murine macrophages a significant increase of cAMP levels at 60 and 120 s. Adenosine, an adenylate cyclase inhibitor, significantly increased the ingestion of latex beads, whereas the combined presence of adenosine and either G-17 or G-34 produced similar values to those of control samples without adenosine or gastrin. These results suggest that gastrin is a negative modulator of several macrophage functions, and that the inhibition of these activities is carried out through an increase of intracellular cAMP levels.

References (33)

J.E. Blalock
Molecular basis for bidirectional communications between the immune and neuroendocrine systems
Physiol. Rev.
(1989)
S.V. Boyden
The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes
J. Exp. Med.
(1962)
M. De la Fuente
Changes in the macrophage function with aging
Comp. Biochem. Physiol. [A]
(1985)
M. De La Fuente et al.
Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C
Immunology
(1991)
M. De la Fuente et al.
Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C
Immunology
(1993)
M. De La Fuente et al.
Stimulation by vasoactive intestinal peptide (VIP) of phagocytic function in rat macrophages. Protein kinase C involvement
Regul. Pept.
(1993)
M. De La Fuente et al.
Stimulation of phagocytic function in mouse macrophages by neurotensin and neuromedin N
J. Neuroimmunol.
(1993)
M. De La Fuente et al.
Inhibition of murine peritoneal macrophage functions by sulfated cholecystokinin octapeptide
Regul. Pept.
(1995)
J.S. Edkins
On the chemical mechanism of gastric secretion
V. Eysselein et al.
Similar acid stimulatory potencies of synthetic human big and little gastrins in man
J. Clin. Invest.
(1984)

G.E. Hatch et al.

Cyclic nucleotic changes in human neutrophils induced by chemoattractants and chemotactic modulators

J. Immunol.

(1977)

A.R. Henderson et al.

Gastric, pancreatic, and intestinal function

C. Isaad et al.

Biphasic regulation of macrophage attachment by activators of cyclic adenosine monophosphate-dependent kinase and protein kinase C

J. Cell Physiol.

(1989)

J. Ishizuka et al.

Effects of gastrin on 3′,5′-cyclic adenosine monophosphate, intracellular calcium and phosphatidylinositol hydrolysis in human colon cancer cells

Cancer Res.

(1994)

D.M. Jensen et al.

Failure of atropine to inhibit gastrin-17 stimulation of the lower esophageal sphincter in man

Gastroenterology

(1978)

M. Martinez et al.

Plasma molecular forms of gastrin, neurotensin in pregnancy and gestational diabetes after oral glucose load or a mixed meal

Regul. Pept.

(1993)

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ArticleModulation of murine peritoneal macrophage functions by gastrin

Abstract

Molecular basis for bidirectional communications between the immune and neuroendocrine systems

Physiol. Rev.

The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes

J. Exp. Med.

Changes in the macrophage function with aging

Comp. Biochem. Physiol. [A]

Modulation of phagocytic function in murine peritoneal macrophages by bombesin, gastrin-releasing peptide and neuromedin C

Immunology

Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C

Immunology

Stimulation by vasoactive intestinal peptide (VIP) of phagocytic function in rat macrophages. Protein kinase C involvement

Regul. Pept.

Stimulation of phagocytic function in mouse macrophages by neurotensin and neuromedin N

J. Neuroimmunol.

Inhibition of murine peritoneal macrophage functions by sulfated cholecystokinin octapeptide

Regul. Pept.

On the chemical mechanism of gastric secretion

Similar acid stimulatory potencies of synthetic human big and little gastrins in man

J. Clin. Invest.

Cyclic nucleotic changes in human neutrophils induced by chemoattractants and chemotactic modulators

J. Immunol.

Gastric, pancreatic, and intestinal function

Biphasic regulation of macrophage attachment by activators of cyclic adenosine monophosphate-dependent kinase and protein kinase C

J. Cell Physiol.

Effects of gastrin on 3′,5′-cyclic adenosine monophosphate, intracellular calcium and phosphatidylinositol hydrolysis in human colon cancer cells

Cancer Res.

Failure of atropine to inhibit gastrin-17 stimulation of the lower esophageal sphincter in man

Gastroenterology

Plasma molecular forms of gastrin, neurotensin in pregnancy and gestational diabetes after oral glucose load or a mixed meal

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Article
Modulation of murine peritoneal macrophage functions by gastrin