Dissociation between cyclic AMP rise and mucin secretion in response to a beta-adrenergic agonist

A novel hypotonic swelling method has been used to introduce cyclic AMP phosphodiesterase (cAMP PDE) into intact rat submandibular acini. Acini swollen in the presence of cAMP PDE showed no cyclic AMP rise in response to the beta-agonist isoproterenol; however, stimulation of mucin secretion was not impaired. Control experiments showed that acini swollen in the absence of cAMP PDE showed normal cyclic AMP rise and mucin secretion responses. The results showing a dissociation between cyclic AMP rise and mucin secretion suggest that cyclic AMP is not the sole mediator of beta-adrenergic stimulation of epithelial cell secretion. The method of intracellular manipulation described will allow (i) investigation of key regulators of secretory events, shown to be defective in CF cells. (ii) determination of the biochemical function of proteins which are candidates for the biochemical defect in CF.