Capacitative Ca²⁺entry is involved in cAMP synthesis in mouse parotid acini

Abstract

Muscarinic receptor interaction leading to augmentation of isoproterenol-stimulated cAMP accumulation in mouse parotid acini involves Ca 2+ (28). The effectiveness of capacitative Ca 2+ entry and intracellular Ca 2+ release on this response was determined in time course studies by using three independent tools to manipulate the free intracellular Ca 2+ concentration: the muscarinic agonist carbachol, thapsigargin, and ionomycin. Time course studies revealed that Ca 2+ release from intracellular stores by carbachol produced an early rapid increase (0.25–0.5 min) in stimulated cAMP levels, whereas capacitative Ca 2+ entry resulted in a sustained increase in stimulated cAMP levels that was blocked by La 3+ . Capacitative Ca 2+ entry, alone, was involved in thapsigargin and ionomycin augmentation of stimulated cAMP accumulation. The inability of phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and milrinone, to prevent agonist augmentation of cAMP levels, as well as the finding that the type VIII adenylyl cyclase (ACVIII) is expressed in parotid acini, suggests that capacitative Ca 2+ entry augments stimulated cAMP accumulation, at least in part, via activation of this adenylyl cyclase isoenzyme.