Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion.
OBJECTIVE
Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release.


METHODS
The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay.


RESULTS
Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion.


CONCLUSIONS
These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.
Sandor
A
A
Gastric Surgical Pathology Research Group, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
Kidd
M
M
Lawton
G P
GP
Miu
K
K
Tang
L H
LH
Modlin
I M
IM
D000109:Acetylcholine / Q000502:physiology; D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002478:Cells, Cultured; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000494:pharmacology / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D013004:Somatostatin / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D018663:Adrenergic Agents; D005755:Gastrins; D005768:Gastrointestinal Hormones; D018377:Neurotransmitter Agents; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine