cAMP- and calcium-mediated modulation of intrinsic factor secretion in isolated rabbit gastric glands

Abstract

We have studied the role of cAMP-mediated and calcium-mediated secretagogues in stimulating secretion of intrinsic factor (IF) from parietal cells in isolated rabbit gastric glands. The magnitudes of IF release caused by maximally stimulating doses of the following agents were compared: histamine (5 x 10(-5) M), forskolin (10(-5) M), 8-bromo-cAMP (10(-3) M), pentagastrin (10(-7) M), carbachol (10(-5) M), and the calcium ionophore A23187 (10(-3) M). Each agent was tested simultaneously in gastric glands prepared from the same animal so as to minimize the effects of variations between preparations. Gastric glands were incubated 30 min alone (unstimulated) or with each of the secretagogues. IF release into the culture medium was measured using an assay based on the binding of IF to 57Co-cyanocobalamin. Results were expressed as percentages IF release above unstimulated levels. Three cAMP-mediated agents significantly (P less than 0.05) stimulated IF secretion above unstimulated levels: histamine (439 +/- 33%), forskolin (769 +/- 385%), and 8-bromo-cAMP (1483 +/- 362%). Two agents thought to act through calcium-dependent mechanisms significantly (P less than 0.05) stimulated IF release: carbachol (79 +/- 25%) and pentagastrin (16 +/- 6%). A23187 did not increase IF release above unstimulated levels (P greater than 0.05). In this study, cAMP-mediated secretagogues stimulated significantly (P less than 0.05) more IF release than carbachol or pentagastrin. This study supports the hypothesis that both cAMP- and calcium-mediated mechanisms participate in regulating IF release.