Activation of purinergic receptors by ATP inhibits secretion in bovine adrenal chromaffin cells

Autoinhibition is a common mechanism observed in neurons to regulate neurot ransmission. Released neurotransmitter interacts with presynaptic autorecep tors to inhibit subsequent release. The requisite elements for autoinhibiti on are present in chromaffin cells: secretory granules contain millimolar l evels of ATP which is coreleased with catecholamines upon stimulation and t he cells express purinergic receptors. We were interested to determine whet her autoinhibition produced by ATP binding to purinergic receptors plays an important role in catecholamine release from chromaffin cells. In these st udies, short depolarizations were used to elicit transmitter release measur ed by membrane capacitance. We find that stimulation of chromaffin cells re sults in the release of endogenous ATP which may suppress Ca2+ channel curr ents and secretion. In the presence of a maximal concentration of ATP, both the amount of secretion and the maximal rate of release are about half tha t observed in the absence of ATP. ATP-mediated inhibition of secretion was blocked by Reactive Blue-2 suggesting the involvement of P-2Y purinergic re ceptors. Prepulses to positive potentials that relieve the Ca2+ channel blo ck largely relieve the inhibition of secretion. Furthermore, when secretion is plotted as a function of Ca2+ influx there is no apparent change in the relationship between control cells and those stimulated in the presence of ATP and prepulses. These results suggest that ATP diminishes secretion by inhibiting Ca2+ influx into the cells. Our results indicate that feedback i nhibition by ATP, mediated primarily by Ca2+ channels, may be an important regulator of catecholamine release in chromaffin cells. (C) 2000 Elsevier S cience B.V. All rights reserved.