Inflammation subtypes

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

T. Kunikata, H. Yamane, E. Segi, T. Matsuoka, Y. Sugimoto, S. Tanaka, H. Tanaka, H. Nagai, A. Ichikawa, S. Narumiya, Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3, Nat. Immunol. 6 (2005) 524. 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

The accumulation of evidence implicating a role for adenosine in the pathogenesis of airway inflammation has led to investigations into all adenosine receptor subtypes as potential therapeutic targets for the treatment of asthma and COPD. To this end, the efficacy of A3AR in the clinical setting has been inconclusive. However, inhibition of Aj and A2B receptors and/or activation of the A2A pathway may serve as an alternative therapeutic approach (Brown et al. 2008b). 

Dixit VD, Schaffer EM, Pyle RS, CoUins GD, Sakthivel SK, Palaniappan R, I.illaid JW, Taub DD (2004) Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J CUn Invest 114 57-66 Dmitrieva N, Shelton D, Rice ASC, McMahon SB (1997) The role of nerve growth factor in a model of visceral inflammation. Neuroscience 78 449-459 Doak GJ, Sawynok J (1997) Formalin-induced nodceptive behavior and edema involvement of multiple peripheral 5-hydroxytryptamine receptor subtypes. Neuroscience 80 939-949 Dobner PR (2006) Neurotensin and pain modulation. Peptides 27 2405-2414 Dobolyi A, Ueda H, Uchida H, Palkovits M, Usdin TB (2002) Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. Proc Natl Acad Sci U S A 99 1651-1656... 

Thiazoles and related analogues have been indicated to influence the inflammatory processes through their antagonistic activity at the adenosine receptors [93-95]. Among the various adenosine receptors, the subtypes Al and A3 have been indicated in inflammation, asthma [96,97], glaucoma [98], myocardial and cerebral ischemia [99-102]. A systematic template search of quinazolines, isoquinolines and other prototypes has resulted in the induction of the thiazole class as adenosine A3 receptor antagonists (Fig. 9) [93]. 

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