Motilin and erythromycin stimulate pepsinogen secretion by chief cells isolated from guinea pig stomach

Abstract

Background: Motilin and erythromycin bind the same receptor in the gastrointestinal muscle cells. Motilin stimulates pepsinogen secretion in humans and dogs. However, it is unclear whether it acts directly on gastric chief cells or via other neurotransmitters. Methods: Isolated gastric chief cells were obtained from guinea pig stomach by collagenase digestion and calcium chelation with ethylene glycol-bis(B-amynomethyl ether)-N,N,N′,N′-tetraacetic acid. Results: Significant stimulation of pespinogen secretion induced by motilin occurred at 1 pmol/L, half maximum at 10 pmol/L, and maximum at 100 pmol/L. Erythromycin caused significant stimulation at 1 pmol/L, half maximum at 100 pmol/L, and maximum at 1 nmol/L. Atropine (1 μmol/L) had no effect on either motilin- or erythromycin-induced pepsinogen secretion. Motilin and erythromycin determined a threefold increase in the intracellular calcium concentrations. Pretreatment of isolated chief cells with motilin and erythromycin induced a reversible, dose- and time-dependent desensitization of the pepsinogen secretion stimulated by carbachol and cholecystokinin but not that stimulated by secretin, vasoactive intestinal peptide, or prostaglandin E2. Conclusions: Motilin and erythromycin directly stimulate pepsinogen secretion in isolated chief cells.