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A mechanistic link between the marine Si cycle and off-axis H2 production requires a reevaluation of the processes that supplied H2 to prebiotic and early microbial systems, as well as those that balanced ocean-atmosphere redox through time.Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa