SIGNAL FLOWS FROM 2 PHOSPHOLIPASE-C LINKED RECEPTORS ARE INDEPENDENT IN PC12 CELLS

Bradykinin (BK) receptor and P-2-purinergic receptor are known to be c oupled to phospholipase C (FLC) in PC12 cells. To study the interactio n between these two PLC-linked receptors, the presence of both recepto rs on individual cells was demonstrated by sequential Ca2+ spikes caus ed by BK and ATP in a single fura-2-loaded cell. BK- and ATP-induced c atecholamine (CA) secretions were desensitized within 5 min. However, in the sequential experiment, the BK-induced homologous desensitizatio n of CA secretion did not block the ATP-induced secretion, and vice ve rsa. Each agonist-induced an increase in inositol 1,4,5-trisphosphate (IP3) production and intracellular free Ca2+ concentration also led to homologous desensitization. However, there was no heterologous desens itization between the two agonists. When the cells were treated with b oth BK and ATP simultaneously, the amounts of CA secretion, IF, produc tion, internal Ca2+ mobilization, and Ca2+ influx were all additive. W e also found that both IP3-induced Ca2+ release from intracellular Ca2 + stores and Ca2+ influx from extracellular space were able to release [H-3]norepinephrine, and the secretion induced by both agonists was e xactly additive in the absence or presence of extracellular Ca2+. The data suggest that the CA secretions caused by BK or ATP may have separ ate secretory pathways even though they activate identical second mess enger pathways.