Decreased levels of adenylate cyclase contribute to the down-regulation of beta-adrenergic signal transduction in the salivary glands of the non-obese diabetic (NOD) mouse.

Stimulation of salivary gland secretion by treatment of NOD mice with the beta-adrenergic receptor agonist, isoproterenol, was previously shown to cause a lower accumulation of intracellular cAMP than that found that in BALB/c controls (Hu et al., 1994, Am. J. Physiol. 266: G433). This was, in part, due to decreased levels of beta-adrenergic receptor localized in the plasma membrane. In the present investigation, basal levels of cAMP in the salivary glands of NOD mice were found to be similar to controls, while direct stimulation of adenylate cyclase by incubation of isolated membranes with forskolin showed a reduced cAMP accumulation in NOD mice versus BALB/c control mice. Using direct [3H]-forskolin binding, it was determined that the plasma membranes of NOD mice salivary glands contain reduced levels of membrane-associated adenylate cyclase.