Mechanism of the inhibitory effect of trifluoperazine on isoprenaline-evoked amylase secretion from isolated rat parotid glands.

We have investigated the effects of the calmodulin antagonist trifluoperazine (TFP) on amylase secretion and adenosine 3':5'-monophosphate (cyclic AMP) metabolism using incubated parotid glands of young rats. Exposing unstimulated glands to 100 microM TFP doubled the basal rate of amylase and lactate dehydrogenase (LDH) release, but had no effect on either the parotid cyclic AMP or ATP contents. Isoprenaline (1 microM) stimulated amylase secretion and increased the tissue cyclic AMP content. 100 microM TFP inhibited these responses by 46% and 33%, respectively. N6,O2-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) mimicked the effect of isoprenaline on amylase release but 100 microM TFP had no effect on this response. 10 microM TFP inhibited F- -stimulated adenylate cyclase activity in a subcellular fraction isolated from the parotid by 32%. We conclude that TFP may inhibit isoprenaline-evoked amylase secretion from the rat parotid by an effect on either the catalytic or regulatory subunits of adenylate cyclase.