RYANODINE RECEPTOR EXPRESSION IS ASSOCIATED WITH INTRACELLULAR CA2-CELLS( RELEASE IN RAT PAROTID ACINAR)

The ryanodine receptor mediates intracellular Ca2+ mobilization in mus cle and nerve, but its physiological role in nonexcitable cells is les s well defined. Like adenosine 3',5'-cyclic monophosphate and inositol 1,4,5-trisphosphate, cyclic ADP-ribose(0.3-5 mu M) and ADP (1-25 mu M ) produced a concentration-dependent rise in cytosolic Ca2+ in permeab ilized rat parotid acinar cells. Adenosine and AMP were less effective . Ryanodine markedly depressed the Ca2+-mobilizing action of the adeni ne nucleotides and forskolin in permeabilized cells and was likewise e ffective in depressing the action of forskolin in intact cells. Cyclic ADP-ribose-evoked Ca2+ release was enhanced by calmodulin and depress ed by W-7, a calmodulin inhibitor. A fluorescently labeled ligand, etr amethyl-4-bora-3,4-diaza-s-indacene-3-propionic acid-glycyl ryanodine, was synthesized to detect the expression and distribution of ryanodin e receptors. In addition, ryanodine receptor expression was detected i n rat parotid cells with a sequence highly homologous to-a rat skeleta l muscle type 1 and a novel brain type 1 ryanodine receptor. These fin dings demonstrate the presence of a ryanodine-sensitive intracellular Ca2+ store in rat parotid cells that shares many of the characteristic s of stores in muscle and nerve and may mediate Ca2+-induced Ca2+ rele ase or a modified form of this process.