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Neurohypophyseal Hormones: From Genomics And Physiology To Disease

Presynaptic actions of endocannabinoids mediate -MSH-induced inhibition of oxytocin cells

Centre for Integrative Physiology, The University of Edinburgh, George Square Edinburgh, United Kingdom

Submitted 13 September 2005 ; accepted in final form 25 October 2005

We recently showed that central injections of -melanocyte-stimulating hormone (-MSH) inhibits oxytocin cells and reduces peripheral release of oxytocin, but induces oxytocin release from dendrites. Dendritic oxytocin release can be triggered by agents that mobilize intracellular calcium. Oxytocin, like -MSH, mobilizes intracellular calcium stores in oxytocin cells and triggers presynaptic inhibition of afferent inputs that is mediated by cannabinoids. We hypothesized that this mechanism might underlie the inhibitory effects of -MSH. To test this, we recorded extracellularly from identified oxytocin and vasopressin cells in the anesthetized rat supraoptic nucleus (SON). Retrodialysis of a CB1 cannabinoid receptor antagonist to the SON blocked the inhibitory effects of intracerebroventricular injections of -MSH on the spontaneous activity of oxytocin cells. We then monitored synaptically mediated responses of SON cells to stimulation of the organum vasculosum of the lamina terminalis (OVLT); this evoked a mixed response comprising an inhibitory component mediated by GABA and an excitatory component mediated by glutamate, as identified by the effects of bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione applied to the SON by retrodialysis. Application of CB1 receptor agonists to the SON attenuated the excitatory effects of OVLT stimulation in both oxytocin and vasopressin cells, whereas -MSH attenuated the responses of oxytocin cells only. Thus -MSH can act as a "switch"; it triggers oxytocin release centrally, but at the same time through initiating endocannabinoid production in oxytocin cells inhibits their electrical activity and hence, peripheral secretion.

dendritic release; supraoptic nucleus; organum vasculosum of the lamina terminalis; presynaptic inhibition; -aminobutyric acid; melanocortin 4 receptor; -melanocyte-stimulating hormone

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