Papaverine stimulation of prostaglandin E₂ production by cultured rabbit gastric mucosa

M. Ligumsky, D. Rachmilewitz, U. Zor

Prostaglandins (PGs) are synthesised by gastric mucosa, and have been shown to inhibit gastric acid secretion and ulcer formation in man and experimental animals. Recently exogenous PGs, mainly of the E group, have been used for the treatment of peptic ulcer disease. We therefore searched for a drug that would stimulate endogenous gastric prostaglandin E₂ (PGE₂) synthesis. Rabbit gastric mucosa slices were cultured for 22 hours at 77°C. PGE₂, measured by radioimmunoassay, was found to be linearly secreted into the culture medium. PGE₂ accumulation in the medium during 22 hours of culture was 7·9±0·5 (SE) ng/mg tissue (N=20). Addition of papaverine (100 µ/ml), a cyclic nucleotide phosphodiesterase inhibitor, resulted in a significant increase (250% of control) in PGE₂ accumulation in the medium: 24·3±1·8 ng/mg tissue (N=25). Isobutylmethylxanthine (IBMX 100 µg/ml), another phosphodiesterase inhibitor, only slightly increased PGE₂ accumulation, while 8 bromo-cyclic AMP (1 mM) had no effect. Under these conditions IBMX increased by 20-fold mucosal cyclic AMP levels: 3·9±0·3 pmol/mg tissue (N=8) as compared with control levels: 0·2±0·03 pmol/mg tissue (N=8). Papaverine, however, did not alter mucosal cyclic AMP accumulation. These results indicate that papaverine stimulates PGE₂ production by cultured rabbit gastric mucosa and that this stimulation is not related to the inhibition of phosphodiesterase activity and accumulation of mucosal cyclic AMP. Papaverine induced stimulation of PGE₂ production should be further evaluated regarding its possible beneficial effects in protecting gastric mucosa and in reducing acid secretion in peptic ulcer patients.

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