Inhibitory effect of somatostatin on Helicobacter pylori proliferation in vitro.
OBJECTIVE
Somatostatin regulates gastric function and cell proliferation. We investigated whether exogenous somatostatin modulates Helicobacter pylori proliferation in vitro.


METHODS
Bacteria were cultured in 5 mL Brucella broth. Bacterial numbers of H. pylori (ATCC 43504) and Escherichia coli were calculated 48 and 5 hours after incubation, respectively, by counting the colonies on the blood agar. Chemicals were dissolved in absolute methanol and added to the broth at a final methanol concentration of 1%. Intrabacterial guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) levels were measured by radioimmunoassay.


RESULTS
Somatostatin significantly suppressed H. pylori proliferation at levels at or above 10(-11) mol/L. A similar antiproliferative effect was observed with 8-bromo-cGMP. At concentrations at or above 10(-8) mol/L, dibutyryl cAMP slightly but significantly stimulated bacterial proliferation. Gastrin had no effect. Somatostatin antibody immunoglobulin G fraction blocked the antiproliferative effect of somatostatin on ATCC 43504. Scatchard plot showed that ATCC 43504 has one class of binding site with relatively high affinity (Kd, 0.31 nmol/L). Somatostatin at 10(-11) mol/L increased cGMP and cAMP in H. pylori 11-fold and 6-fold, respectively. In contrast, somatostatin neither bound E. coli nor affected its proliferation.


CONCLUSIONS
Somatostatin, at a similar level in human gastric juice (approximately 10(-11) mol/L), suppresses H. pylori proliferation mediated in part by a cGMP-dependent pathway in vitro, indicating a possible inhibitory effect of somatostatin in the gastric lumen on H. pylori proliferation in humans.
Yamashita
K
K
Fourth Department of Internal Medicine, Aichi Medical University, Aichi, Japan.
Kaneko
H
H
Yamamoto
S
S
Konagaya
T
T
Kusugami
K
K
Mitsuma
T
T
D000906:Antibodies / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016480:Helicobacter pylori / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D013004:Somatostatin / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D001426:Bacterial Proteins; D013004:Somatostatin; D000242:Cyclic AMP; D006152:Cyclic GMP