CELL-SPECIFIC PURINERGIC RECEPTORS COUPLED TO CA2- DIFFERENTIAL SENSITIVITY TO UTP AND SURAMIN( ENTRY AND CA2+ RELEASE FROM INTERNAL STORESIN ADRENAL CHROMAFFIN CELLS )

We have assessed the relative contribution of Ca2+ entry and Ca2+ rele ase from internal stores to the [Ca2+](i) transients evoked by puriner gic receptor activation in bovine adrenal chromaffin cells. The [Ca2+] (i) was recorded from single cells using ratiometric fura-2 microfluor ometry. Two discrete groups of ATP-sensitive cells could be distinguis hed on the basis of their relative capacity to respond to ATP in the v irtual absence of extracellular Ca2+. One group of cells (group I) fai led to respond to ATP in the absence of Ca2+, was completely insensiti ve 60 UTP, and displayed suramin-blockable [Ca2+](i) transients when c hallenged with ATP in the presence of external Ca2+. ATP activated a p rominent and rapidly inactivating Mn2+ influx pathway in group I cells , as assessed by monitoring Mn2+ quenching of fura-2 fluorescence. In contrast, a second group of ATP-sensitive cells (group II) exhibited p ronounced [Ca2+](i) rises when challenged with ATP and UTP in the abse nce of Ca2+ and was completely insensitive to suramin, ATP and UTP act ivated a delayed and less prominent Mn2+ influx pathway in group II ce lls, Contrary to the nicotinic receptor agonist DMPP, which evoked a p referential release of epinephrine, ATP evoked a preferential release of norepinephrine, and UTP had no effect on secretion. Suramin nearly suppressed ATP-evoked norepinephrine release. We conclude that chromaf fin cells contain two distinct and cell-specific purinoceptor subtypes . Although some cells express a P-2U-type purinoceptor coupled to Ca2 release from internal stores and to the associated slow Ca2+ refillin g mechanism, other cells express a suramin-sensitive and UTP insensiti ve purinoceptor exclusively coupled to Ca2+ influx, probably an ATP ga ted channel. It is suggested that the ATP-gated channel is preferentia lly localized to norepinephrine-secreting chromaffin cells and support s specifically hormone output from these cells. Thus, the biochemical pathways involved in the exocytotic release of the two major stress-re lated hormones appear to be regulated by distinct signaling systems.