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YANNICK GOUMON Y COLS. AN. R. ACAD. NAC. FARM.

binding protein (PEBP) which would prevent it being cleared via the
kidneys. Our findings also showed that, in the chromaffin cell model,
M6G is the final product of the alkaloid synthesis pathway, and
could represent a neuroendocrine effector.

A number of studies conducted on invertebrate immune cells
have shown that morphine synthesis is stepped up at times of stress
(55). More recently, a number of articles have reported that immune
cells [notably polymorphonuclear cells and monocytes (68, 112)]
synthesise morphine, pointing to a role in immune responses.

The intensive use of morphine in hospitals has spurred many
studies focusing on the presence of morphine in the serum or plasma
after the i.v. administration of exogenous morphine. In contrast to
this body of work on exogenous morphine, there is little information
about endogenous morphine in the blood although some findings
suggest that endogenous morphine may play a role in stress and
immune responses. Since the beginning of the 1990’s, a number of
studies on invertebrate immune cells had demonstrated morphine
synthesis in response to stress (55). Three other studies conducted
on pigs and patients who had undergone invasive surgery (e.g.
coronary bypass surgery or laparotomy) showed elevated levels of
endogenous morphine in the blood. Tonnesen et al. showed that
coronary bypass surgery induced a rise in the amount of morphine
in human serum from 0.28 nM to 3.9 nM (113-115) and, in another
experiment, the same group measured a morphine concentration of
about 10 nM in the blood of piglets who had undergone coronary
bypass surgery while none was detectable in control animals (113).
Finally, a human study suggested that the concentration of morphine
in the blood was higher after open cholecystectomy than it was after
laparascopy (0.2 nM versus 0.018 nM) (115). Surgical procedures
such as bypass surgery or thoracotomy elicit massive inflammation,
e.g. the extracorporeal circulation associated with coronary bypass
surgery always causes inflammation. Taken together, these
observations point to a link between rises in blood morphine and
inflammation. It is interesting to note that estimated IC50’s for µ
receptors [of the order of 10 nM (116)] are consistent with the levels
observed in the circulation, suggesting that endogenous morphine
may have effects on different cell types, including immune cells and
endothelial cells.

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