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Purinergic modulation of Ca 2+ channels and exocytosis in bovine chromaffin cells
Author(s) -
Ulate Guido,
Scott Steve Richard,
Gilabert Juan Antonio,
Artalejo Antonio R.
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1102
Subject(s) - purinergic receptor , exocytosis , chromaffin cell , microbiology and biotechnology , neurotransmitter , purinergic signalling , biology , adrenal medulla , p2y receptor , ppads , chemistry , adenosine , biophysics , secretion , endocrinology , receptor , biochemistry , catecholamine , adenosine receptor , agonist
It 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 neurotransmitter release by acting on presynaptic purinoceptors of the P2Y type. The mechanisms underlying inhibition of neurotransmission by P2Y purinoceptors may involve either inhibition of membrane excitability, particularly Ca 2+ entry through voltage‐activated Ca 2+ 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 Ca 2+ regulated exocytosis; 2) ATP binds to P2Y purinergic receptors to inhibit Ca 2+ channels; and 3) they are amenable to combined capacitance measurement and voltage clamp recordings for the purpose of directly examining the relationship between voltage‐activated Ca 2+ entry and exocytosis. This paper reviews our recently published results on the specific Ca 2+ channel types that are inhibited by ATP and their relative contribution to the expected ATP regulation of catecholamine release from bovine chromaffin cells. While no direct effect of ATP on the secretory machinery could be evidenced, ATP regulation of exocytosis is voltage‐dependent as a reflection of the voltage dependence of ATP effects on Ca 2+ channels. These data lend support to the idea of an ATP‐mediated autocrine regulation of secretion from chromaffin cells, though feed‐back regulation of the rate of release can be assumed to be a complex function of the occupancy of the purinoceptors and the electrical and secretory activity of the cell. Drug Dev. Res. 52:89–94, 2001. © 2001 Wiley‐Liss, Inc.