Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla

  title={Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla},
  author={Stefanie Hofer and William T. Ralvenius and Mar{\'i}a Salom{\'e} Gachet and Jean-Marc Fritschy and Hanns Ulrich Zeilhofer and J{\"u}rg Gertsch},

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

The discussion on the current knowledge of the pharmacological effects, the biosynthesis of the peptide cannabinoids and the new insights on the activation and modulation of cannabinoid receptors by these peptides are focused on.

Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage

It is shown that pepcan-12 acts as a potent hCB2 receptor positive allosteric modulator (PAM), which significantly potentiated the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for [35S]GTPγS binding and cAMP inhibition (5–10 fold).

Hemopressin as a breakthrough for the cannabinoid field

Modulation of Noradrenergic and Serotonergic Systems by Cannabinoids: Electrophysiological, Neurochemical and Behavioral Evidence.

It is proposed that interaction between the endocannabinoid system and the noradrenergic-serotonergic systems could account for some of the anxiolytic, antidepressant, and antinociceptive effects of cannabinoids or the disruption of attention/sleep induced by these drugs.

Characterization of pepcan-23 as pro-peptide of RVD-hemopressin (pepcan-12) and stability of hemopressins in mice.

Disordered Peptides Looking for Their Native Environment: Structural Basis of CB1 Endocannabinoid Receptor Binding to Pepcans

While disordered in aqueous environment, both peptides display helical structure in less polar environment, mimicking the proteic receptor milieu, which opens the way to structure-driven design of selective peptide modulators of CB1.

Synthetic Cannabinoid Receptor Agonists and Antagonists: Implication in CNS Disorders.

An overview of CB1 and CB2 receptor synthetic ligands obtained from drug research and in particular those synthesized for therapeutic purposes and potential clinical applications for central nervous system disorders is provided.



Modulation of the endocannabinoid system in cardiovascular disease: therapeutic potential and limitations.

In the absence of a cellular storage mechanism for endocannabinoids, their tissue levels are determined by the balance between the rate of their “on-demand” synthesis and their enzymatic degradation.

Identification of proopiomelanocortin neurones in rat hypothalamus by in situ cDNA-mRNA hybridization

The anatomical co-localization of PomC-related peptides and POMC-specific mRNAs to a single major cell group in the medial basal hypothalamus is reported, providing strong support for POMM biosynthesis within brain tissue.

Identification and Quantification of a New Family of Peptide Endocannabinoids (Pepcans) Showing Negative Allosteric Modulation at CB1 Receptors*

Pepcans are the first endogenous allosteric modulators identified for CB1 receptors and could play an important physiological role in modulating endocannabinoid signaling.

Role of endogenous cannabinoids in synaptic signaling.

The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation, and the fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release.

Why do cannabinoid receptors have more than one endogenous ligand

How anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis is discussed.

The major central endocannabinoid directly acts at GABAA receptors

The identification of a functional binding site for 2-AG in the GABAA receptor may have far-reaching consequences for the study of locomotion and sedation.

The Role of the Endocannabinoid System in the Regulation of Hypothalamic‐Pituitary‐Adrenal Axis Activity

  • D. Cota
  • Biology
    Journal of neuroendocrinology
  • 2008
Observations suggest that alterations of the endocannabinoid tone might be associated with the development of stress‐related diseases, including anxiety, depression and obesity.

Opposing local effects of endocannabinoids on the activity of noradrenergic neurons and release of noradrenaline: relevance for their role in depression and in the actions of CB1 receptor antagonists

Both neuronal activation and neurotransmitter release depend on the in situ synthesized endocannabinoids and thus, local endoc cannabinoidoid concentrations in different brain areas may be crucial in the net effect, namely in the regulation of neurons located postsynaptically to the noradrenergic synapse.

Structure of a cannabinoid receptor and functional expression of the cloned cDNA

The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.

The endocannabinoid system and the brain.

Research on the actions of the endocannabinoid system on anxiety, depression, neurogenesis, reward, cognition, learning, and memory, and the effects are at times biphasic--lower doses causing effects opposite to those seen at high doses.