The present studies were directed to examine the effects of beta-adrenergic and cholinergic stimulation on gastrin release and to assess the potential role of gastrin-releasing peptide in exerting these effects, utilizing incubated rat antral mucosa. Rat antral mucosa was incubated at 37 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, continuously gassed with 95% O2-5% CO2. After 1 h media were sampled for radioimmunoassay measurement of gastrin content. Inclusion of carbachol (2.5 X 10(-6) M) in culture medium increased medium gastrin concentration by 106 +/- 28% (P less than 0.01); addition of specific antibodies to gastrin-releasing peptide to the culture medium did not affect carbachol-stimulated gastrin release. Inclusion of isoproterenol (10(-9) M) in culture medium did not affect somatostatin release into the medium, but increased medium gastrin by 234 +/- 24% (P less than 0.001). However, in contrast to carbachol, addition of antibodies to gastrin-releasing peptide to culture medium decreased isoproterenol-stimulated gastrin release by 67 +/- 9% (P less than 0.001). Results of these studies indicate that, under the conditions of these experiments, beta-adrenergic, but not muscarinic, stimulation of gastrin release may be mediated, at least in part, through gastrin-releasing peptide.