Norepinephrine-induced inositol 1,4,5-trisphosphate formation in atrial myocytes is regulated by extracellular calcium, protein kinase C, and calmodulin.

We investigated whether alteration of extracellular and intracellular Ca2+ concentrations. protein kinase C, and calmodulin modulate norepinephrine(NE)-induced inositol 1.4.5-trisphosphate (IP3) formation in neonatal rat atrial myocytes. NE-induced IP3 production ill atrial myocytes was stimulated by elevation of extracellular Ca2+ in a dose-dependent manner. However. TMB-8 (all intracellular calcium antagonist) and A23187 (an intracellular calcium agonist) (lid not significantly affect NE-induced IP3 production. PMA (a protein kinase C agonist) significantly decreased and staurosporine (a protein kinase C antagonist) significantly stimulated NE-induced IP3 production. W7 (a calmodulin antagonist) significantly increased the NE-induced IP3. In conclusion. elevation of extracellular Ca2+ concentrations affects NE-induced IP3 formation in atrial myocytes. Protein kinase C and calmodulin may control the IP3 response to NE by a negative feedback mechanism.