Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue

doi:10.1016/0016-5085(92)91505-X

Gastroenterology

Volume 103, Issue 4, October 1992, Pages 1207-1214

https://doi.org/10.1016/0016-5085(92)91505-X Get rights and content

Abstract

Somatostatin receptors were evaluated in four human gut-associated lymphoid tissues (palatine tonsils, ileal Peyer patches, vermiform appendix, and colonic solitary lymphatic follicles) using receptor autoradiography on tissue sections incubated with ¹²⁵I[Tyr³]octreotide. All four tissues were somatostatin-receptor positive; the receptors were preferentially located in the germinal centers, with the luminal part of the center more strongly labeled than the basal part. The corona of the follicles and the primary follicles without germinal centers did not display somatostatin receptors. The receptors were of high affinity (K_d = 1.3 ± 0.6 nmol/L) and specific for somatostatin. Displacement by nanomolar concentrations of somatostatin 14, somatostatin 28, and octreotide was observed, as was guanosine triphosphate dependency. The gastrointestinal mucosa and the plexus submucosus and myentericus also contained somatostatin receptors. These data strongly suggest that the germinal centers of the gut-associated lymphoid tissue are a site of action of somatostatin. It possibly mediates antiproliferative effects and inhibits immunoglobulin synthesis in the activated lymphoid cells. The human gut represents a multifaceted target for somatostatin action, in which at least three different tissues (mucosa, nerve plexus, and lymphoid tissue) are involved.

References (48)

GE Hermann et al.
Modulation of IgA synthesis by neuroendocrine peptides
Trends Endocrinol Metab
(1991)
SP Sreedharan et al.
Distinct subsets of somatostatin receptors on cultured human lymphocytes
J Biol Chem
(1989)
JC Reubi et al.
Distribution of somatostatin receptors in the human brain: an autoradiographic study
Neuroscience
(1986)
JC Reubi et al.
Distribution of somatostatin receptors in normal and tumor tissue
Metabolism
(1990)
J DelValle et al.
Cellular mechanisms of somatostatin action in the gut
Metabolism
(1990)
K Dharmsathaphorn et al.
Somatostatin inhibits fluid secretion in the rat jejunum
Gastroenterology
(1980)
JC Reubi et al.
Different ionic requirements for somatostatin receptor subpopulations in the brain
Regul Pept
(1986)
JC Reubi et al.
Autoradiographic mapping of somatostatin receptors in the rat CNS and pituitary
Neuroscience
(1985)
DG Payan et al.
Inhibition by somatostatin of the proliferation of T-lymphocytes and Molt-4 lymphoblasts
Cell Immunol
(1984)
RN Mascardo et al.
Somatostatin has an antiproliferative effect on concanavalin A activated rat thymocytes
Clin Immunol Immunopathol
(1984)

S Fais et al.

Effects of somatostatin on human intestinal lamina propria lymphocytes. Modulation of lymphocyte activation

J Neuroimmunol

(1991)

Y Elitsur et al.

Gastrointestinal neuropeptides suppress human colonic lamina propria lymphocyte DNA synthesis

Peptides

(1990)

JC Reubi

Evidence for two somatostatin-14 receptor types in rat brain cortex

Neurosci Lett

(1984)

JC Reubi et al.

Distinct topographical localisation of two somatostatin receptor subpopulations in the human cortex

Brain Res

(1987)

J Epelbaum

Somatostatin in the central nervous system: physiology and pathological modifications

Prog Neurobiol

(1986)

J Polak et al.

Growth-hormone release-inhibiting hormone in gastrointestinal and pancreatic D cells

Lancet

(1975)

LI Larsson

Gastrointestinal cells producing endocrine, neurocrine and paracrine messenger

Clin Gastroenterol

(1980)

F Sundler et al.

Peptidergic nervous systems in the gut

Clin Gastroenterol

(1980)

DG Payan et al.

Neuroimmunology

Adv Immunol

(1986)

AM Stanisz et al.

Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferation by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen

J Immunol

(1986)

DG Payan et al.

Modulation of lymphocyte function by sensory neuropeptides

J Immunol

(1985)

R Scichittano et al.

Distribution of somatostatin receptors on murine spleen and Peyer's patch T and B lymphocytes

Brain Behav Immun

(1987)

JC Reubi et al.

Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas

Cancer Res

(1990)

B Sordat et al.

Differentiation pathway within germinal centers

Adv Exp Med Biol

(1969)

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Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue

Abstract

Trends Endocrinol Metab

J Biol Chem

Neuroscience

Metabolism

Metabolism

Gastroenterology

Regul Pept

Neuroscience

Cell Immunol

Clin Immunol Immunopathol

J Neuroimmunol

Peptides

Neurosci Lett

Brain Res

Prog Neurobiol

Lancet

Clin Gastroenterol

Clin Gastroenterol

Adv Immunol

Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferation by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen

J Immunol

Modulation of lymphocyte function by sensory neuropeptides

J Immunol

Distribution of somatostatin receptors on murine spleen and Peyer's patch T and B lymphocytes

Brain Behav Immun

Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas

Cancer Res

Differentiation pathway within germinal centers

Adv Exp Med Biol