TY - JOUR T1 - P2Y Purinoceptors Inhibit Exocytosis in Adrenal Chromaffin Cells via Modulation of Voltage-Operated Calcium Channels JF - The Journal of Neuroscience JO - J. Neurosci. SP - 606 LP - 616 DO - 10.1523/JNEUROSCI.20-02-00606.2000 VL - 20 IS - 2 AU - Andrew D. Powell AU - Anja G. Teschemacher AU - Elizabeth P. Seward Y1 - 2000/01/15 UR - http://www.jneurosci.org/content/20/2/606.abstract N2 - We have used combined membrane capacitance measurements (Cm) and voltage-clamp recordings to examine the mechanisms underlying modulation of stimulus–secretion coupling by a Gi/o-coupled purinoceptor (P2Y) in adrenal chromaffin cells. P2Y purinoceptors respond to extracellular ATP and are thought to provide an important inhibitory feedback regulation of catecholamine release from central and sympathetic neurons. Inhibition of neurosecretion by other Gi/o-protein-coupled receptors may occur by either inhibition of voltage-operated Ca2+ channels or modulation of the exocytotic machinery itself. In this study, we show that the P2Y purinoceptor agonist 2-methylthio ATP (2-MeSATP) significantly inhibits Ca2+ entry and changes inCm evoked by single 200 msec depolarizations or a train of 20 msec depolarizations (2.5 Hz). We found that P2Y modulation of secretion declines during a train such that only ∼50% of the modulatory effect remains at the end of a train. The inhibition of both Ca2+ entry and ΔCm are also attenuated by large depolarizing prepulses and treatment with pertussis toxin. Inhibition of N-type, and to lesser extent P/Q-type, Ca2+channels contribute to the modulation of exocytosis by 2-MeSATP. The Ca2+-dependence of exocytosis triggered by either single pulses or trains of depolarizations was unaffected by 2-MeSATP. When Ca2+ channels were bypassed and exocytosis was evoked by flash photolysis of caged Ca2+, the inhibitory effect of 2-MeSATP was not observed. Collectively, these data suggest that inhibition of exocytosis by Gi/o-coupled P2Y purinoceptors results from inhibition of Ca2+ channels and the Ca2+ signal controlling exocytosis rather than a direct effect on the secretory machinery. ER -