Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation.

• Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experimental models. We have analysed the expression and function of CCK-B/gastrin receptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short-term (5 days) histamine2-receptor blockade (loxtidine) resulted in increased histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mucosa. This increase was significantly and dose-dependently reversed by selective CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hypergastrinemia, induced by histamine2-receptor blockade, gave rise to ECL cell carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated in ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor blockade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals reduces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids. These results demonstrate that HDC mRNA expression in neoplastic ECL cells is not controlled by CCK-B/gastrin receptors.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Animals

Benzodiazepines

pharmacology

Carcinoid Tumor

genetics

metabolism

pathology

Cell Transformation

Neoplastic

Enterochromaffin Cells

metabolism

Gastric Mucosa

metabolism

Gastrins

blood

Gene Expression

Histamine H2 Antagonists

pharmacology

Histidine Decarboxylase

genetics

Hormone Antagonists

pharmacology

Humans

Muridae

RNA

Messenger

genetics

metabolism

RNA

Neoplasm

genetics

metabolism

Receptors

Cholecystokinin

metabolism

Stomach Neoplasms

genetics

metabolism

pathology

Triazoles

pharmacology

Publication and Content Type

ref (subject category)

art (subject category)