Chemical characterization and regulation of endogenous morphine and codeine in the rat. J Pharmacol Exp Ther

Data on the tissue distribution of morphine and codeine in rat are presented. The concentration of these two opiate alkaloids seems to be distributed uniformly in the cortex, midbrain, pons/ medulla and cerebellum. The spinal cord and the adrenal gland have high levels of morphine and codeine and the adrenal has more codeine than morphine. The major fractlon of the alkaloids reside in a synaptosomal fraction and are present in tissues as the sulfate conjugate. The levels of morphine in the spinal cord and the urinary excretion of morphine are elevated in the arthritic rat model. We used extracted alkaloid samples from arthritic rats spinal cord for analysis by mass spectrometry and found molec-ular ions identical with morphine and codeine. The results are discussed in the light of possible physiological roles of endoge-nous morphine and codeine. The finding by our group of endogenous morphine and co-deine in mammalian tissues and the ability of those tissues to synthesize the alkaloids (Donnerer et aL, 1986) leads to many questions. One is the tissue distribution of the endogenous alkaloids and the correlation between quantitative determina-tion by RIA and mass spectrometer. A major challenge is to establish the physiological roles of each of the opiate alkaloids, their subcellular distributions and in what form, free or conju-gated, they reside in tissues. The phenolic group of morphine can be either conjugated as a glucuronide or sulfated by the enzyme phenolsulfotransferase (Rein et aL, 1982). It is also possible that morphine exists in tissues bound to protein (Misra et aL, 1971). This paper addresses some of these questions