Purinergic modulation of Ca2+ channels and exocytosis in bovine chromaffincells

is now firmly established that adenosine 5'-triphosphate (ATP) can act as a fast excitatory neurotransmitter by activation of postsynaptic purinergic receptors. Moreover, ATP also serves as a neuromodulator and inhibits neuro transmitter release by acting on presynaptic purinoceptors of the P2Y type. The mechanisms underlying inhibition of neurotransmission by P2Y purinocep tors may involve either inhibition of membrane excitability, particularly C a2+ entry through voltage-activated Ca2+ channels, or direct action on the secretory apparatus. Bovine chromaffin cells from the adrenal medulla are a good model system to address this problem since: 1) they store and release ATP along with catecholamines by Ca2+ regulated exocytosis; 2) ATP binds t o P2Y purinergic receptors to inhibit Ca2+ channels; and 3) they are amenab le to combined capacitance measurement and voltage clamp recordings for the purpose of directly examining the relationship between voltage-activated C a2+ entry and exocytosis. This paper reviews our recently published results on the specific Ca2+ channel types that are inhibited by ATP and their rel ative contribution to the expected ATP regulation of catecholamine release from bovine chromaffin cells. While no direct effect of ATP on the secretor y machinery could he evidenced, ATP regulation of exocytosis is voltage-dep endent as a reflection of the voltage dependence of ATP effects on Ca2+ cha nnels. These data lend support to the idea of an ATP-mediated autocrine reg ulation of secretion from chromaffin cells, though feed-back regulation of the rate of release can be assumed to be a complex function of the occupanc y of the purinoceptors and the electrical and secretory activity of the cel l. Drug Dev. Res. 52:89-94, 2001. (C) 2001 Wiley-Liss, Inc.