Adrenergic and cromolyn sodium modulation of ECL cell histamine secretion.
The histamine secreting enterochromaffin-like (ECL) cell is now recognized as the principal regulator of gastric acid secretion. Histamine is not only a primary modulator of acid secretion, but may be of relevance in gastritis and as a mitogen in gastric neoplasia. Study of the ECL cell has been limited since no pure preparation was available. We therefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin immunofluorescence. Trypan blue exclusion demonstrated > 95% viability. While gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delineated. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanisms of histamine secretion, we evaluated the mast cell histamine inhibitor sodium cromoglycate. Histamine secretion was determined by radioimmunoassay. Basal secretion was 0.6 +/- 0.2 nmol/10(3) cells. Gastrin stimulated histamine secretion with an EC50 of 3 x 10(-10) M. Octopamine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulated histamine secretion (EC50, 6 x 10(-8) M) and was inhibited by propranolol (IC50 5 x 10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Lawton
G P
GP
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520.
Tang
L H
LH
Miu
K
K
Gilligan
C J
CJ
Absood
A
A
Modlin
I M
IM
D000262:Adenylyl Cyclases / Q000378:metabolism; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013564:Sympathetic Nervous System / Q000502:physiology*
D018663:Adrenergic Agents; D005755:Gastrins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004205:Cromolyn Sodium