Dynorphin - Temperature Regulation

Temperature Regulation

In addition to their role in weight control, dynorphins have been found to regulate body temperature. Opioid peptides were first investigated in hyperthermia, where it was found that MOR agonists stimulate this response when injected into the periaqueductal gray (PAG) region of the brain. Xin et al. showed that delivery of dynorphin A_1-17 (a KOR agonist) through microdialysis into the PAG region induced hypothermia in rats. The authors found that the severity of hypothermia was proportional to the dose of dynorphin A_1-17 administered. Hypothermia could be prevented by administering KOR antagonist norBNI to the rat. Xin et al. hypothesized that while MOR agonists mediate hyperthermia, KOR agonists, such as dynorphin, mediate hypothermia.

Sharma and Alm found that subjecting rats to heat (38˚C) caused dynorphins to be upregulated in the cerebral cortex, hippocampus, cerebellum, and the brain stem. Further, authors found that administration of nitric oxide synthase (NOS) inhibitors reduced dynorphin A1-17 levels in the brain and attenuated symptoms related to heat stress. Sharma and Alm concluded that hyperthermia increases dynorphin levels, which may cause damage and promote heat stress reaction. They further hypothesized that nitric oxide was part of this mechanism. Ansonoff et al. found that hypothermic effects are mediated through K1 (κ-opioid receptor 1), but not K2. The authors applied a KOR agonist to K1 knockout mice, which eliminated hypothermic response. Thus, K2 does not appear to have a role in the hypothermic mechanism