Human platelets express authentic CB₁ and CB₂ receptors.
In the last decade, the neurovascular effects exerted by endocannabinoids (eCBs) have attracted growing interest, because they hold the promise to open new avenues of therapeutic intervention against major causes of death in Western society. Several actions of eCBs are mediated by type-1 (CB₁) or type-2 (CB₂) cannabinoid receptors, yet there is no clear evidence of the presence of these proteins in platelets. To demonstrate that CB₁ and CB₂ are expressed in human platelets, we analyzed their protein level by Western blotting and ELISA, visualized their cellular localization by confocal microscopy, and ascertained their functionality by binding assays. We found that CB₁, and to a lesser extent CB₂, are expressed in highly purified human platelets. Both receptor subtypes were predominantly localized inside the cell, thus explaining why they might remain undetected in preparations of plasma membranes. The identification of authentic CB₁ and CB₂ in human platelets supports the potential exploitation of selective agonists or antagonists of these receptors as novel therapeutics to combat neurovascular disorders. It seems remarkable that some of these substances have been already used in humans to treat disease states.
Catani
M V
MV
Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy. mmaccarrone@unite.it
Gasperi
V
V
Catanzaro
G
G
Baldassarri
S
S
Bertoni
A
A
Sinigaglia
F
F
Avigliano
L
L
Maccarrone
M
M
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D001892:Camphanes / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003511:Cyclohexanols / Q000493:pharmacokinetics; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D010976:Platelet Count; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D014316:Tritium / Q000493:pharmacokinetics; D055815:Young Adult
D001892:Camphanes; D003511:Cyclohexanols; D039661:Integrin beta3; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D014316:Tritium; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D000077285:Rimonabant; D002118:Calcium