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Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain
Author(s) -
Hirasawa Michiru,
Schwab Yannick,
Natah Sirajedin,
Hillard Cecilia J.,
Mackie Ken,
Sharkey Keith A.,
Pittman Quentin J.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.066159
Subject(s) - am251 , endocannabinoid system , chemistry , cannabinoid receptor , neuroscience , cannabinoid , neuropeptide , agonist , pharmacology , receptor , biology , biochemistry
Oxytocin is released from supraoptic magnocellular neurones and is thought to act at presynaptic receptors to inhibit transmitter release. We now show that this effect is mediated by endocannabinoids, but that oxytocin nonetheless plays an important role in endocannabinoid signalling. WIN55,212‐2, a cannabinoid receptor agonist, mimicked the action of oxytocin and occluded oxytocin‐induced presynaptic inhibition. The cannabinoid action is at the presynaptic terminal as shown by alteration in paired pulse ratio, a reduction in miniature EPSC frequency and immunohistochemical localization of CB 1 receptors on presynaptic terminals. AM251, a CB 1 receptor antagonist, blocked both the WIN55,212‐2 and the oxytocin‐induced presynaptic inhibition of EPSCs. Depolarization of postsynaptic magnocellular neurones (which contain fatty acid amide hydrolase, a cannabinoid catabolic enzyme) caused a transient inhibition of EPSCs that could be blocked by both the AM251 and Manning compound, an oxytocin/vasopressin receptor antagonist. This indicates that somatodendritic peptide release and action on previously identified autoreceptors facilitates the release of endocannabinoids that act as mediators of presynaptic inhibition.