Forskolin stimulation of acid and pepsinogen secretion by gastric glands

Isolated gastric glands were used to investigate the action of forskolin, a novel diterpene extracted from the Indian plant Coleus forskohlii. Forskolin was found to stimulate both acid formation and pepsinogen secretion. The stimulation was rapid, reversible and dose dependent with an ED50 of approx. 1 microM. The efficacy of forskolin was similar to that of more commonly used secretagogues, e.g. histamine, carbachol, cyclic AMP derivatives. The responses to forskolin were not inhibited by any of the receptor-specific antagonists tested. Forskolin activated adenyl cyclase in gland homogenates over a dose range similar to that required for stimulation of secretory activity. Forskolin was found to be more effective in activating adenyl cyclase than histamine, isoproterenol or NaF. Treatment of gastric glands with forskolin resulted in a 100-fold increase in tissue cAMP levels, supporting the idea that forskolin activates adenyl cyclase in the intact cell. The results are interpreted to show that forskolin stimulation of gastric secretions is due to activation of adenyl cyclase with a consequent increase in tissue cAMP.