ArticleThe Journal of biological chemistry2012
Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 162 citations in OpenAlex.
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- Molecular insights into the inhibition of angiotensin-converting enzyme 1 by hemopressin peptides.Scientific reports · 2024Article
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Comparative targeted lipidomics between serum and cerebrospinal fluid of multiple sclerosis patients shows sex and age-specific differences of endocannabinoids and glucocorticoids.Acta neuropathologica communications · 2024Article
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker.Biomolecules · 2024Article
- Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.International journal of molecular sciences · 2024Review
- Discovery and development of macrocyclic peptide modulators of the cannabinoid 2 receptor.The Journal of biological chemistry · 2024Article
- Hemoglobin α-derived peptides VD-hemopressin (α) and RVD-hemopressin (α) are involved in electroacupuncture inhibition of chronic pain.Frontiers in pharmacology · 2024Article
- Methods for Intracellular Peptidomic Analysis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study.Biomolecules · 2023Article
- The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans.Current biology : CB · 2023Article
- Article
- Effects of Prenatal Cannabinoids Exposure upon Placenta and Development of Respiratory Neural Circuits.Advances in experimental medicine and biology · 2023Review
- Endocannabinoid signaling in astrocytes.Glia · 2023Review
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Metabolic Messengers: endocannabinoids.Nature metabolism · 2022Review
- Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The α-hemoglobin-derived dodecapeptide RVD-hemopressin (RVDPVNFKLLSH) has been proposed to be an endogenous agonist for the cannabinoid receptor type 1 (CB(1)). To study this peptide, we have raised mAbs against its C-terminal part. Using an immunoaffinity mass spectrometry approach, a whole family of N-terminally extended peptides in addition to RVD-Hpα were identified in rodent brain extracts and human and mouse plasma. We designated these peptides Pepcan-12 (RVDPVNFKLLSH) to Pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH), referring to peptide length. The most abundant Pepcans found in the brain were tested for CB(1) receptor binding. In the classical radioligand displacement assay, Pepcan-12 was the most efficacious ligand but only partially displaced both [(3)H]CP55,940 and [(3)H]WIN55,212-2. The data were fitted with the allosteric ternary complex model, revealing a cooperativity factor value α < 1, thus indicating a negative allosteric modulation. Dissociation kinetic studies of [(3)H]CP55,940 in the absence and presence of Pepcan-12 confirmed these results by showing increased dissociation rate constants induced by Pepcan-12. A fluorescently labeled Pepcan-12 analog was synthesized to investigate the binding to CB(1) receptors. Competition binding studies revealed K(i) values of several Pepcans in the nanomolar range. Accordingly, using competitive ELISA, we found low nanomolar concentrations of Pepcans in human plasma and ∼100 pmol/g in mouse brain. Surprisingly, Pepcan-12 exhibited potent negative allosteric modulation of the orthosteric agonist-induced cAMP accumulation, [(35)S]GTPγS binding, and CB(1) receptor internalization. Pepcans are the first endogenous allosteric modulators identified for CB(1) receptors. Given their abundance in the brain, Pepcans could play an important physiological role in modulating endocannabinoid signaling.
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