Malcher-Lopes et al. provide electrophysiological and biochemical evidence for a signaling pathway that begins with glucocorticoid stimulation of endocannabinoid synthesis via a Gas-cAMP-PKA pathway, and which is countered by leptin via phosphodiesterase 3B-mediated reduction of cAMP levels. This action takes places in the hypothalamic paraventricular nucleus (PVN). At stake is endocannabinoid-mediated retrograde inhibition of synaptic responses onto PVN magnocellular and parvocellular neurons. The authors show that the action of glucocorticoids is rapid and nongenomic, involving a membrane receptor. The action of leptin involves the Ob-Rb leptin receptor leading through a series of kinases to activation of phosphodiesterase 3B.

What are the consequences?
Well, in response to fasting, for example, there is a decrease in leptin levels, an increase in glucocorticoids, and activation of CB1 cannabinoid receptors, leading to hypothalamic stimulation of feeding. The signaling pathway outlined by the authors seems well positioned to regulate energy homeostasis, fluid balance, and the stress response.

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Renato Malcher-Lopes, Shi Di, Victor S. Marcheselli, Feng-Ju Weng, Christopher T. Stuart, Nicolas G. Bazan, and Jeffrey G. Tasker

News tip from The Journal of Neuroscience

Contact: Sara Harris
Society for Neuroscience