The chondroitin ABC lyase digestion products of normal human femoral condyle articular cartilage and of purified aggrecan were analyzed for their mono-and nonsulfated disaccharide composition. Changes in the total tissue chemistry were most pronounced during the period from birth to 20 years of age, when the -[GlcA␤,3GalNAc6]-disaccharide content increased from approximately 50% to 85% of the total disaccharide content and there was a concomitant decrease in the content of the 4-sulfated disaccharide. In general, the disaccharide content of the deeper layers of immature cartilage were richer in the 4-sulfated residue than the upper regions of the tissue. As the tissue aged and decreased in thickness, the disaccharide composition became more evenly 6-sulfated. The newly synthesized chondroitin sulfate chains had a similar composition to the endogenous chains and also underwent the same age and zonal changes. The monoclonal antisera 3B3(؉) and 2B6(؉) were used to immunolocalize the unsaturated 6-and 4-sulfated residues generated at the reducing termini of the chondroitin sulfate chains by digestion with chondroitin ABC lyase, and these analyses indicated that the sulfation pattern at this position did not necessarily reflect the internal disaccharide composition of the chains. In summary, the sulfation pattern of chondroitin sulfate disaccharides from human normal articular cartilage varies with the age of the specimen, the position (topography) on the joint surface, and the zone of cartilage analyzed. Furthermore, these changes in composition are a consequence of both extracellular, post-translational processing of the core protein of aggrecan and changes in the sulfotransferase activity of the chondrocyte.Proteoglycans are major components of the extracellular matrix of articular cartilage and provide the tissue with many of its characteristic physicochemical properties, including its ability to generate an osmotic swelling pressure, which enables it to withstand a wide range of compressive loads (1). Proteoglycans are also known to directly influence chondrocyte activity, either through cell-matrix interactions or by binding specific growth factors in the extracellular matrix, thereby modifying their temporal and spatial effects. Many of these biological interactions are properties of the glycosaminoglycan chains, which are covalently attached to the protein cores of individual proteoglycan molecules. In articular cartilage, the glycosaminoglycans are mainly chondroitin and keratan sulfate chains, as well as a small proportion of dermatan sulfate chains, and they exert their action by virtue of the high electronegative charge and spatial arrangement of their constituent sulfate groups.Aggrecan, the major type of proteoglycan found in articular cartilage, consists of a protein core to which are attached many chondroitin sulfate chains that are predominantly 4-or 6-sulfated (2). Aging of human articular cartilage is accompanied by many changes in the structure of aggrecan and the multimolecular aggregate that it ...

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Clonidine is an adrenergic agonist with high affinity for alpha2 adrenoceptors that also has affinity for imidazoline receptors. Clonidine has previously been shown to reduce immobility in the forced swim test (FST) in mice. In the present study, this effect was blocked by idazoxan (0.06 mg/kg s.c.) and by yohimbine (1.0 mg/kg s.c.) suggesting that clonidine's effects in this test are mediated via its action at alpha2 sites. Imidazoline I2 site ligands have been shown to inhibit monoamine oxidase and thus may also have antidepressant activity. Three compounds with selective affinity for I2 receptors (BU224, BU239, BDF 8082) were also tested in the FST. These compounds showed no activity either alone or in combination with a subthreshold dose of imipramine in the FST. These results suggest that I2 receptor ligands do not show antidepressant-like activity in the FST in mice. Furthermore the activity of the mixed alpha2/I1 agonist clonidine is most likely to be due to its action at alpha2 sites.

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