Isoproterenol potentiates α-adrenergic and muscarinic receptor-mediated Ca2+ response in rat parotid cells

The effects of the cAMP pathway on the Ca2+ response elicited by phospholipase C-coupled receptor stimulations were studied in rat parotid cells. Although 1 μM isoproterenol (Iso) itself had no effect on the cytosolic Ca2+ concentration, the pretreatment with Iso potentiated Ca2+ responses evoked by phenylephrine. The potentiating effect of Iso was attributed to a shifting of the concentration-response curves of phenylephrine to the left and an increase in the maximal response. Half-maximal potentiation occurred at 3 nM Iso. Iso also potentiated the Ca2+ response elicited by carbachol. The potentiating effect of Iso was mimicked by forskolin (10 μM) and dibutyryl adenosine 3′,5′-cyclic monophosphate (2 mM) and was blocked by 10 μM H-89. Iso potentiated the phenylephrine-induced Ca2+response in the absence of extracellular Ca2+, but Iso did not increase the inositol trisphosphate (IP3) production induced by phenylephrine. These results suggest that the potentiation of the Ca2+ response can be attributed to a sensitization of IP3 receptors by cAMP-dependent protein kinase.