Symplified model for inhibitory regulation of epinephrine secretion involving transmitters released from both nerve terminals and chromaffin cells. Auto-inhibitory feedback loops related to cholinergic transmission are not considered for simplicity. Inhibitory transmitters acting on receptors preferentially located to adrenergic chromaffin cells (i.e. P2Y receptors (this work) and κ-opioid receptors ) have been considered, as well as norepinephrine which inhibits epinephrine release via α2C-adrenoceptors . Activation of P2Y, κ-opioid and α2-adrenergic receptors inhibits voltage-sensitive Ca2+ channels via Gi/o proteins (not depicted for the latter two receptors for simplicity) and, consequently, exocytosis [4,9,10,12-14,40-45]. Protein kinase C is negatively coupled to VSCCs in an isoform-specific fashion . AD-cell: adrenergic chromaffin cell; NA-cell: noradrenergic chromaffin cell; Ach: acetylcholine; VSCC: voltage-sensitive Ca2+ channels; AchR: nicotinic cholinergic receptors; P2XR: P2X receptors; P2YR: P2Y receptors; κ-OpiR/α2AdrR: κ-opioid and α2-adrenergic receptors (represented as a single entity for simplicity); PLC: phospholipase C; PKC: protein kinase C; Gq and Gi/o: G proteins; Epi: epinephrine; Norepi: norepinephrine; Opi: opioid peptides. For simplicity, and because [Ca2+]i rises induced by PLC activation do not evoke catecholamine secretion from bovine chromaffin cells, they are not made explicit in the scheme. Also for simplicity, granule exocytosis is not depicted as occurring preferentially in the vicinity of VSCC hot-spots. Positive and negative signs indicate stimulatory and inhibitory interactions, respectively.