Forskolin, a tool for rat parotid secretion studies: 45Ca efflux is not related to cAMP.

In the present work, we investigated, by use of forskolin, whether adenosine 3',5'-cyclic monophosphate (cAMP) level and Ca movements were modulated sequentially or in parallel by the activation of the beta-adrenergic receptor in the rat parotid gland. Forskolin-induced [3H]protein secretion was dependent on external Ca, whereas isoproterenol-induced secretion was not. This effect was not due to a requirement of adenylate cyclase for Ca, since the cAMP level increase induced by forskolin was not Ca dependent. Furthermore isoproterenol induced 45Ca efflux, whereas forskolin did not. 45Ca efflux was correlated neither to cAMP nor to secretion, since when there was a massive augmentation of cAMP there was no change in 45Ca efflux, and forskolin, which induced much secretion, was unable to induce Ca efflux. Carbachol potentiated the secretion induced by forskolin in the absence of Ca, whereas it did not potentiate the isoproterenol-induced response. From these results we suggest that beta-adrenergic receptor activation would lead to two parallel events, cAMP accumulation and Ca movements, which together would lead to maximal secretion.