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VOL. 75 (3), 389-418, 2009 CENTRAL AND PERIPHERAL ENDOGENOUS MORPHINE

of mammalian species. The adrenal gland is one of the major organs
involved in responses to stress and is composed of a cortical part
(where glucocorticoids are produced) and a medullary part [mainly
composed of chromaffin cells (107-109)]. Previously, morphine had
also been found in PC-12 cells which are transformed rat chromaffin
cells (66, 110), and in eel chromaffin cells (111). Chromaffin cells are
neuroendocrine cells derived from the neural crest which are full
of secretory granules containing catecholamines together with many
different proteins and peptides, including chromogranins (107). In
a stressful situation, chromaffin cell stimulation by the splanchnic
nerve induces membrane depolarisation and degranulation which
leads to emptying of catecholamines and the other granule contents
into the blood stream. It is worth noting that the catecholamines
(dopamine, adrenaline and noradrenaline) are all derived from
dopamine and tyrosine precursors, as is morphine.

In experiments carried out in 2006 in a bovine chromaffin cell
model, we detected M6G inside these cells’ secretory granules (Figure
6). M6G secretion was also observed when nicotine was used to
induce depolarisation in these cells in primary tissue culture.
Because these chromaffin cells degranulate in response to stress, it
is likely that M6G is secreted along with the catecholamines in such
responses. Once in the circulation, the M6G could bind µ receptors
on diverse cell types (immune cells, endothelial cells, etc.) and trigger
physiological responses. We also showed that the M6G in chromaffin
granules is stored as a complex with phosphatidylethanolamine-

Figure 6. Confocal laser micrograph showing primary chromaffin cells in
tissue cells labelled with antibodies against morphine and CGA (a granular
marker). Colocalisation highlighted in yellow.

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