Medical College of Wisconsin
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Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain. J Physiol 2004 Sep 01;559(Pt 2):611-24

Date

07/16/2004

Pubmed ID

15254151

Pubmed Central ID

PMC1665137

DOI

10.1113/jphysiol.2004.066159

Scopus ID

2-s2.0-4644280012 (requires institutional sign-in at Scopus site)   127 Citations

Abstract

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 CB1 receptors on presynaptic terminals. AM251, a CB1 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.

Author List

Hirasawa M, Schwab Y, Natah S, Hillard CJ, Mackie K, Sharkey KA, Pittman QJ

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Autocrine Communication
Benzoxazines
Brain
Cannabinoid Receptor Modulators
Dendrites
In Vitro Techniques
Male
Morpholines
Naphthalenes
Neurons, Afferent
Neurotransmitter Agents
Nifedipine
Rats
Rats, Sprague-Dawley