Our hypothesis is that fundamental opiate signaling processes exist and evolved in invertebrate neural tissues and have been evolutionarily retained in humans. This is supported by our preliminary findings that invertebrates produce an endogenous morphine-like material and have mu3 opiate receptors which are indistinguishable from the human counterpart. The experiments in this proposal are designed to identify morphine itself, clone the mu3 receptor in the invertebrate nervous system and directly relate these findings to a function test, i.e., morphine stimulated calcium transients. We propose to address the following objectives: What is the role of the opiate alkaloid, i.e., morphine in the invertebrate nervous system and what does it tell us about the human system? The experiments in this proposal are designed to answer these questions. We propose to develop this hypothesis with the neural tissues of the marine bivalve Mytilus edulis, making it a model for this analysis. More specifically, these studies test our hypothesis that opiate signaling, transcending pain functions, evolved in invertebrates to diminish sensory inputs, and that because this system worked so well, it was retained during evolution. Given this growing documentation for endogenous morphine in neural signaling the potential for its involvement in psychiatry is becoming evident.

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College at Old Westbury
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Nieto-Fernandez, F; Andrieux, S; Idrees, S et al. (2009) The effect of opioids and their antagonists on the nocifensive response of Caenorhabditis elegans to noxious thermal stimuli. Invert Neurosci 9:195-200
Stefano, George B; Kream, Richard M; Mantione, Kirk J et al. (2008) Endogenous morphine/nitric oxide-coupled regulation of cellular physiology and gene expression: implications for cancer biology. Semin Cancer Biol 18:199-210
Cheng, Jeanette; Zhang, Chen; Han, Ji-Sheng et al. (2007) TENS stimulates constitutive nitric oxide release via opiate signaling in invertebrate neural tissues. Med Sci Monit 13:BR163-7
Stefano, George B; Bianchi, Enrica; Guarna, Massimo et al. (2007) Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: the dopamine-morphine hypothesis. Med Sci Monit 13:RA91-102
Stefano, George B; Kream, Richard M (2007) Endogenous morphine synthetic pathway preceded and gave rise to catecholamine synthesis in evolution (Review). Int J Mol Med 20:837-41
Pryor, Stephen C; Nieto, Fernando; Henry, Sherwyn et al. (2007) The effect of opiates and opiate antagonists on heat latency response in the parasitic nematode Ascaris suum. Life Sci 80:1650-5
Mantione, Kirk J; Kim, Celline; Stefano, George B (2006) Morphine regulates gill ciliary activity via coupling to nitric oxide release in a bivalve mollusk: opiate receptor expression in gill tissues. Med Sci Monit 12:BR195-200
Esch, Tobias; Kim, Jae Won; Stefano, George B (2006) Neurobiological implications of eating healthy. Neuro Endocrinol Lett 27:21-33
Kream, Richard M; Stefano, George B (2006) De novo biosynthesis of morphine in animal cells: an evidence-based model. Med Sci Monit 12:RA207-19
Stefano, George B; Fricchione, Gregory L; Esch, Tobias (2006) Relaxation: molecular and physiological significance. Med Sci Monit 12:HY21-31

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