European journal of pharmacology
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Paclitaxel is an effective chemotherapeutic agent, but has some treatment-limiting adverse effects that markedly decrease patients' quality of life. Peripheral neuropathy is one of these, and no treatment for it has been established yet. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted from the stomach and has widespread effects on multiple systems. ⋯ Both ghrelin-null mice and growth hormone secretagogue receptor-null mice developed more severe nerve injuries than wild-type mice. Our results suggest that ghrelin administration exerts a protective effect against paclitaxel-induced neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions, and that endogenous ghrelin has a neuroprotective effect that is mediated by ghrelin/growth hormone secretagogue receptor signaling. Ghrelin could be a promising therapeutic agent for the management of this intractable disease.
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Orexins are important regulators of cardiovascular functions in various physiological and pathological conditions. The dorsomedial hypothalamus (DMH), an essential mediator of cardiovascular responses to stress, contains dense orexinergic innervations and receptors. We examined whether orexins can regulate cardiovascular functions through their actions in the DMH in anesthetized rats. ⋯ In a series of experiment, effects of orexin B (100pmol) and then orexin A (30pmol), were examined at a same site. Two patterns of responses were observed in 12 intra-DMH sites: (1) both orexin A and B (9 sites), and (2) only orexin A (3 sites) induced cardiovascular responses, respectively suggesting OX1R/OX2R-mediated and OX1R-predominant mechanisms. In conclusion, orexins regulated cardiovascular functions through OX1R/OX2R- or OX1R-mediated mechanisms at different locations in the DMH.