Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Br J Pharmacol. 2010 Jun;160(3):677-87. doi: 10.1111/j.1476-5381.2010.00756.x.
The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders.
We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist.
THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg.kg(-1) i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg.kg(-1), and in both phases of this test at 5 mg.kg(-1); these effects of THCV appeared to be CB(1) and CB(2) receptor mediated.
THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation.
植物大麻素，Delta(9)-四氢大麻素（THCV）可以阻断大麻素 CB(1) 受体。本研究旨在探讨其激活 CB(2) 受体的能力，因为有证据表明，联合 CB(2) 激活/CB(1) 阻断将改善某些疾病。
我们通过确定以下几点来测试 THCV 激活 CB(2) 受体的能力：（i）它是否抑制转染人 CB(2)（hCB(2)）受体的中国仓鼠卵巢（CHO）细胞中福斯柯林刺激的环 AMP 产生；（ii）它是否刺激 [(35)S]GTPγS 与 hCB(2)CHO 细胞和小鼠脾膜结合；（iii）它是否减轻由角叉菜胶或甲醛注射到小鼠后爪引起的炎症/痛觉过敏迹象；以及（iv）任何此类抗炎或抗痛觉过敏作用是否被 CB(1) 或 CB(2) 受体拮抗剂阻断。
THCV 抑制 hCB(2)CHO 细胞中环 AMP 的产生（EC(50)=38 nM），但不抑制 hCB(1)或未转染的 CHO 细胞，也不抑制预先用百日咳毒素（100 ng.mL(-1)）孵育并刺激 [(35)S]GTPγS 与 hCB(2)CHO 和小鼠脾膜结合的 hCB(2)CHO 细胞。THCV（0.3 或 1 mg.kg(-1) 腹腔注射）以似乎是 CB(2) 受体介导的方式降低角叉菜胶诱导的水肿，并抑制角叉菜胶诱导的痛觉过敏。THCV（腹腔注射）还降低了福氏佐剂测试第二阶段 1 mg.kg(-1)时的疼痛行为，以及该测试两个阶段 5 mg.kg(-1)时的疼痛行为；THCV 的这些作用似乎是通过 CB(1)和 CB(2)受体介导的。
THCV 可以在体外激活 CB(2) 受体，并在一定程度上通过 CB(1) 和/或 CB(2) 受体激活来减轻小鼠的炎症和炎症性疼痛迹象。
