Protein kinase C inhibitors enhance endothelin‐1 and attenuate vasopressin and angiotensin II evoked [Ca²⁺]_i elevation in the rat cardiomyocyte

Primary cultures of neonatal rat cardiomyocytes were pretreated for 16 h with either nonselective (staurosporine, 100 nm) or selective (NPC15437, 20 μm) protein kinase C (PKC) inhibitors. These inhibitors did not affect the basal cytosolic free calcium, [Ca²⁺]_i, level (106 ± 12 nm) as determined by fura‐2 fluorescence methodology. Both agents significantly enhanced the maximal [Ca²⁺]_i responses to endothelin‐1 (ET‐1) and attenuated the peak [Ca²⁺]_i responses to arginine vasopressin and angiotensin II. They did not alter the EC₅₀ values of any of these agonists. Since depletion of [Ca²⁺]_o led to only partial attenuation of the enhanced response to ET‐1 in the treatment groups, it is likely that PKC inhibition results in an exaggerated intracellular mobilization of Ca²⁺ to ET‐1. It is concluded that PKC modulates agonist(s)‐evoked intracellular Ca²⁺ mobilization and that the nature of regulation is governed by the agonist. 1993 British Pharmacological Society