ADRENERGIC AND CROMOLYN SODIUM MODULATION OF ECL CELL HISTAMINE-SECRETION

The histamine secreting enterochromaffin-like (ECL) cell is now recogn ized as the principal regulator of gastric acid secretion. Histamine i s not only a primary modulator of acid secretion, but may be of releva nce in gastritis and as a mitogen in gastric neoplasia. Study of the E CL cell has been limited since no pure preparation was available. We t herefore developed a pure isolated ECL cell preparation with a purity of 90-95% as determined by total histamine content and chromogranin im munofluorescence. Trypan blue exclusion demonstrated >95% viability. W hile gastrin and acetylcholine are known modulators of acid secretion, the role of adrenergic neurotransmitters has not been clearly delinea ted. The purpose of this study was to examine adrenergic modulation of ECL cell histamine release. To further define the inhibitory mechanis ms of histamine secretion, we evaluated the mast cell histamine inhibi tor sodium cromoglycate. Histamine secretion was determined by radioim munoassay. Basal secretion was 0.6 +/- 0.2 nmol/10(3) cells. Gastrin s timulated histamine secretion with an EC(50) of 3 X 10(-10) M. Octopam ine (alpha-adrenergic agonist) (10(-11)-10(-4) M) failed to stimulate histamine secretion. Isoproterenol (beta-adrenergic agonist) stimulate d histamine secretion (EC(50), 6 X 10(-8) M) and was inhibited by prop ranolol (IC50 5 X 10(-10) M). Sodium cromoglycate inhibited isoprotere nol (IC50 10(-7) M) and gastrin (IC50 10(-8) M). Isoproterenol resulte d in an increase of ECL cell cAMP which was not inhibited by sodium cr omoglycate. These data are consistent with the presence of a beta-adre nergic. but not an alpha-adrenergic, receptor on the ECL cell and sugg ests a role of the adrenergic neural system in the modulation of ECL c ell function. The effect of the mast cell histamine release inhibitor suggests a common mechanism for histamine release by both mast cells a nd ECL cells. (C) 1995 Academic Press, Inc.