Dear Editor, For centuries, morphine has been used for several medicinalpurposes, however in modern medicine it is widely use for managing pain. It was originally thought tobe produced by certain types of plants, but recent evidence has shown it to also be produced endogenouslyby animal tissues [1]. Besides its analgesic effect, morphine has other biological effects. In particular,it has been shown to be involved in endocrine, vascular, immune and respiratory functions [2-5]. Sincethe endocrine system interacts with the nervous system in regulating many organ systems activities ofthe body, morphine also appears to be acting like a hormone. Stefano and colleagues have identified endogenousmorphine in animal nervous tissues, as well as in rat adrenal medullary chromaffin PC-12 cells [6,7].The adrenal glands, located above each of the two kidneys, consist of an outer cortex and an inner medulla.Normally, the adrenal medulla secretes the hormone epinephrine, also known as adrenaline, into the bloodafter receiving sympathetic nerve innervation. In addition, corticosteroids, including cortisol, arealso released by the adrenal cortex affecting glucose balance. A recent study by Yannick Goumon et al.has demonstrated the presence of a morphine-like molecule inside the bovine chromaffin cell secretorygranules, which was also detected in the secretion medium of primary chromaffin cells in culture followingnicotinic stimulation [8]. Their findings demonstrated that a morphine-like compound is synthesized inchromaffin cells and is secreted into the incubation medium upon stimulation. This finding indicatesthat this morphine-like material may be released from adrenal tissues, in response to stressors, andbehaving like a hormone. Regarding brain endocrine structures, according to Lewczuk et al., morphinedoes not directly affect activity of the pineal gland in immature pigs; however, it may affect the secretionof melatonin indirectly by causing an increase in the sensitivity of the tissue involved with melatoninsynthesis and secretion in the presence of light [9]. Other studies have shown interspecies differencesin the effects of opiates on melatonin secretion. Karasek et al. states that in various types of tumorsalterations in melatonin concentrations have been observed, and that melatonin therapy has been reportedhelpful in advanced cancer of various types [10]. Finally, in a study by Sewerynek et al.., it has beenshown that melatonin decreased the concentration of molecules involved with oxidative stress (conjugateddienes, malondialdehude, Schiff bases) in the kidneys of male rats with thyrotoxicosis [11]. In anotherstudy by Sewerynek et al., they have shown melatonin to be involved in reducing blood pressure and decreasedcatecholamine level after 90 min in human subjects [12]. The reduced blood pressure by melatonin mayoccur by a direct effect on the hypothalamus, as an antioxidant, which lowers blood pressure, by decreasingthe level of catecholamines, or by relaxing the smooth muscle in the aorta wall. Overall, it appearsthat there is a correlation between morphine and melatonin in various biological activities involvedwith protection of the animal. References: 1.Cadet P, Mantione K, Bilfinger TV, Stefano GB: Morphinedown regulates human vascular tissue estrogen receptor expression determined by real-time RT-PCR. NeuroendocrinolLett, 2002; 23: 95-100 2.Stefano GB, Zhu W, Cadet P et al: A hormonal role for endogenous opiate alkaloids:Vascular tissues. Neuroendocrinology Letters, 2002; 23: 21-26 3.Esch T, Guarna M, Bianchi E et al: Commonalitiesin the central nervous system's involvement with complementary medical therapies: Limbic morphinergicprocesses. Med Sci Monit, 2004; 10(6): MS6-MS17 4.Esch T, Stefano GB: The neurobiology of pleasure, rewardprocesses, addiction and their health implications. Neuroendocrinology Letters, 2004; 25: 235-51 5.EschT, Stefano GB: The Neurobiology of Love. Neuroendo-crinology Letters, 2005; In press 6.Goumon Y, WeeksBS, Cadet P, Stefano GB: Identification of morphine in the adrenal medullary chromaffin PC-12 cell line.Mol Brain Res, 2000; 81: 177-80 7.Zhu W, Baggerman G, Goumon Y et al: Identification of morphine andmorphine-6-glucuronide in the adrenal medullary chromaffin PC-12 cell line by nano electrospray ionizationdouble quadrupole orthogonal acceleration time of flight mass spectrometry. Eur J of Mass Spect, 2001;7: 25-28 8.Goumon Y, Strub JM, Stefano GB et al: Characterization of a morphine-like molecule in secretorygranules of chromaffin cells. Med Sci Monit, 2005; 11(5): MS31-MS34 9.Lewczuk B, Przybylska-GornowiczB, Wyrzykowski Z: The effect of morphine on melatonin secretion in the domestic pig. In vivo and in vitrostudy. Neuroendocrinol Lett, 1999; 20: 171-78 10.Karasek M, Pawlikowski M: Pineal gland, melatonin andcancer. NEL Review. Neuroendocrinol Lett, 1999; 20: 139-44 11.Sewerynek E, Wiktorska J, Lewinski A: Effectsof melatonin on the oxidative stress induced by thyrotoxicosis in rats. Neuroendocrinol Lett, 1999; 20:157-61 12.Sewerynek E: Melatonin and the cardiovascular system. Neuro Endocrinol Lett, 2002; 23(Suppl.1):79-83.

Keywords: Melatonin - pharmacology, Morphine - pharmacology, Neurosecretory Systems - metabolism