The possible participation of prostaglandin (PG) E₂ in angiogenesis in the granulation tissue was analyzed using an air pouch-type carrageenin-induced inflammation model in rats. Injection of carrageenin solution into a pre-formed air pouch on the dorsum induced the increase in the pouch fluid volume, the granulation tissue formation and the angiogenesis in the granulation tissue. The cyclooxygenase (COX) -2 inhibitor NS-398 as well as the COX-1/COX-2 inhibitor indomethacin inhibited all of these parameters, suggesting that COX-2 plays a role in angiogenesis in addition to inflammatory responses. The increase in protein levels of vascular endothelial growth factor (VEGF) in the supernatant fraction of the pouch fluid was inhibited by treatment with NS-398 or indomethacin. To clarify the role of PGE₂ in VEGF production, the minced granulation tissue was incubated in the presence of various concentrations of PGE₂. It was shown that PGE₂ (0.01-1 μM) increased VEGF protein levels in the conditioned medium of the minced granulation tissue and VEGF mRNA levels in the minced granulation tissue in a concentration-dependent manner. These findings suggest that COX-2-derived PGE₂ plays a significant role in angiogenesis in the carrageenin-induced granulation tissue through VEGF formation. The mechanism by which PGE₂ induces VEGF production is discussed.

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Cannabinoids, psychoactive components in marijuana, bind to G protein-coupled cannabinoid receptors expressed in the brain and other tissues, and exert a variety of neural and peripheral actions. Two arachidonic acid derivatives, anandamide (N-arachidonoylethanolamine) and 2-arachi-donoylglycerol, are known to be endogenous ligands of cannabinoid receptors and are collectively referred to as endocannabinoids. Both the endocannabinoids are enzymatically formed from membrane glycerophospholipid upon cellular stimuli, and then rapidly degraded. The compounds exhibit various biological activities through cannabinoid receptors including reduction of cyclic AMP, inhibition of voltage-gated calcium channels and cannabimimetic behavioral activities. The'endocannabinoid system' comprising endocannabinoids, cannabinoid receptors and enzymes involved in the biosynthesis and degradation of endocannabinoids currently receives considerable attention as promising therapeutic targets.

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