Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage
| Autor: | Vanessa Petrucci, Zongxian Cao, Sandra Glasmacher, Andrea Chicca, Jürg Gertsch, Pal Pacher, János Pálóczi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cannabinoid receptor Allosteric modulator medicine.medical_treatment Allosteric regulation lcsh:Medicine 610 Medicine & health Biology Article Receptor Cannabinoid CB2 03 medical and health sciences chemistry.chemical_compound Hemoglobins Structure-Activity Relationship Allosteric Regulation Tandem Mass Spectrometry Internal medicine Adrenal Glands medicine Cannabinoid receptor type 2 Metabolomics Receptor lcsh:Science Multidisciplinary lcsh:R Endocannabinoid system Hemopressin Peptide Fragments 030104 developmental biology Endocrinology chemistry Liver Reperfusion Injury Metabolome 570 Life sciences biology lipids (amino acids peptides and proteins) lcsh:Q Cannabinoid Chromatography Liquid Protein Binding |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) Scientific Reports Petrucci, Vanessa; Chicca, Andrea; Glasmacher, Sandra Patricia; Paloczi, Janos; Cao, Zongxian; Pacher, Pal; Gertsch, Jürg (2017). Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage. Scientific Reports, 7(1), p. 9560. Nature Publishing Group 10.1038/s41598-017-09808-8 |
| ISSN: | 2045-2322 |
| Popis: | Pepcan-12 (RVD-hemopressin; RVDPVNFKLLSH) is the major peptide of a family of endogenous peptide endocannabinoids (pepcans) shown to act as negative allosteric modulators (NAM) of cannabinoid CB1 receptors. Noradrenergic neurons have been identified to be a specific site of pepcan production. However, it remains unknown whether pepcans occur in the periphery and interact with peripheral CB2 cannabinoid receptors. Here, it is shown that pepcan-12 acts as a potent (K i value ~50 nM) hCB2 receptor positive allosteric modulator (PAM). It 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). In mice, the putative precursor pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH) was identified with pepcan-12 in brain, liver and kidney. Pepcan-12 was increased upon endotoxemia and ischemia reperfusion damage where CB2 receptors play a protective role. The adrenals are a major endocrine site of production/secretion of constitutive pepcan-12, as shown by its marked loss after adrenalectomy. However, upon I/R damage pepcan-12 was strongly increased in the liver (from ~100 pmol/g to ~500 pmol/g) independent of adrenals. The wide occurrence of this endogenous hormone-like CB2 receptor PAM, with unforeseen opposite allosteric effects on cannabinoid receptors, suggests its potential role in peripheral pathophysiological processes. |
| Databáze: | OpenAIRE |
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