Endogenous codeine: autocrine regulator of catecholamine release from chromaffin cells

In addition to the catecholamines (CAs) dopamine (DA), norepinephrine (NE) and epinephrine (E), perifused chromaffin cells of the eel secrete codeine and morphine. In controls, the release of NE and E is strongly correlated, while there is no correlation with DA. Low, physiological concentrations of codeine (500 pg/ml) reduce the release of NE and E, while 8-fold higher concentrations stimulate an instant, transitory release of all three CAs. Much higher concentration of codeine (100 ng/ml), corresponding to the therapeutically effective range in the human, again reduce the release of NE and E. Physiological and very high concentrations of morphine have no clear effect on CA release, while an intermediate concentration (38 ng/ml) increases the secretion of all three CAs. The opiate antagonist naloxone lowers the basal CA secretion and prevents the morphine-induced CA increase. During naloxone perifusion, a normally non-effective concentration (40 ng/ml) of codeine reduces the CA release. It appears that codeine is an autocrine regulator which suppresses CA release via naloxone-insensitive receptors, and stimulates CA release via opiate receptor(s). Co-released morphine may modulate the action of codeine.