The cannabinomimetic arachidonyl‐2‐chloroethylamide (ACEA) acts on capsaicin‐sensitive TRPV<sub>1</sub> receptors but not cannabinoid receptors in rat joints
Bibliographic record
Abstract
The vasoactive effects of the synthetic cannabinoid (CB) arachidonyl-2-chloroethylamide (ACEA) was tested in the knee joints of urethane-anaesthetised rats. Experiments were also performed to determine whether these vasomotor responses could be blocked by the selective CB(1) receptor antagonists AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) (10(-9) mol) and AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) (10(-8) mol), as well as the selective CB(2) receptor antagonist AM630 (6-iodo-2-methyl-1-[2-4(morpholinyl)ethyl]-[1H-indol-3-yl](4-methoxyphenyl)methanone) (10(-8) mol). Peripheral application of ACEA (10(-14)-10(-9) mol) onto the exposed surface of the knee joint capsule caused a dose-dependent increase in synovial blood flow. The dilator action of the CB occurred within 1 min after drug administration and rapidly returned to control levels shortly thereafter. The maximal vasodilator effect of ACEA corresponded to a 30% increase in articular perfusion compared to control levels. The hyperaemic action of ACEA was not significantly altered by coadministration of AM251, AM281 or AM630 (P>0.05; two-way ANOVA). The transient receptor potential channel vanilloid receptor 1 (TRPV(1)) antagonist capsazepine (10(-6) mol) significantly reduced the vasodilator effect of ACEA on joint blood vessels (P=0.002). Furthermore, destruction of unmyelinated and thinly myelinated joint sensory nerves by capsaicin (8-methyl-N-vanillyl-6-nonenamide) treatment also attenuated ACEA responses (P<0.0005). These data clearly demonstrate a vasodilator effect of the cannabinomimetic ACEA on knee joint perfusion. Rather than a classic CB receptor pathway, ACEA exerts its vasomotor influence by acting via TRPV(1) receptors located on the terminal branches of capsaicin-sensitive afferent nerves innervating the joint.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".