Lack of prostaglandin involvement in the mitogenic effect of TSH on canine thyroid cells in primary culture.

The production of prostaglandin E2 (PGE2) by cultured dog thyroid cells was high in a serum-containing medium and low in a serum-free, completely defined medium. Thyrotropin (TSH) and epidermal growth factor (EGF), two mitogenic factors for these cells, did not stimulate PGE2 release. Indomethacin, at a concentration which completely inhibited PGE2 production, had no effect on thyroid cell multiplication and DNA synthesis stimulated by TSH and EGF. It is concluded that cyclooxygenase products are not involved in the proliferation of canine thyroid cells and its control by TSH.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

The purinergic receptor P2Y(2) receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation.

Background:  Extracellular ATP contributes to the pathogenesis of asthma via signalling at purinergic receptors. However, the precise purinergic receptors subtypes mediating the pro-asthmatic effects of ATP have not been identified, yet. Methods:  In vivo studies were performed using the OVA-alum model. Functional expression of the P2Y(2) purinergic receptor subtype on human monocyte-derived dendritic cells and eosinophils was investigated using real-time PCR, migration assays, and production of reactive oxygen species. Results:  Compared to wild-type animals P2Y(2) -/- mice showed reduced allergic airway inflammation which can be explained by defective migration of blood myeloid DCs towards ATP in vitro and in vivo, whereas the influence of ATP on maturation and cytokine production was not changed. Additionally, ATP failed to induce migration of bone marrow-derived eosinophils from P2Y(2) R-deficient animals. The relevance of our findings for humans was confirmed in functional studies with human monocyte-derived DCs and eosinophils. Interestingly, stimulation of human DCs derived from allergic individuals with house dust mite allergen induced functional up-regulation of the P2Y(2) R subtype. Furthermore, eosinophils isolated from asthmatic individuals expressed higher levels of P2Y(2) R compared to healthy controls. This was of functional relevance as these eosinophils were more sensitive to ATP-induced migration and production of reactive oxygen metabolites. Conclusions:  In summary, P2Y(2) R appears to be involved in asthmatic airway inflammation by mediating ATP-triggered migration of mDCs and eosinophils, as well as reactive oxygen species production. Together our data suggest that targeting P2Y(2) R might be a therapeutic option for the treatment of asthma

The recently deorphanized GPR80 (GPR99) proposed to be the P2Y15 receptor is not a genuine P2Y receptor

The members of the International Union of Pharmacol. (IUPHAR) Subcommittee for P2Y receptor nomenclature and classification carefully examd. the report of Inbe et al. (2004), entitled "Identification and characterization of a cell-surface receptor, P2Y15 for AMP and adenosine" and of He et al. (2004), entitled "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" to establish whether or not to accept GPR80/GPR99 as the P2Y15 receptor. It was concluded that the results of Inbe et al. were more likely to be due to high levels of expression of endogenous adenosine receptors in the clone of HEK293 cells expressing GPR80/GPR99, and/or to heterodimer formation or another artifact. Thus, the P2Y Receptor Nomenclature Subcommittee has decided that GPR80/GPR99 is not a P2Y receptor for adenosine, AMP or other nucleotides, but instead is activated by citric acid cycle intermediates. To avoid confusion in P2Y receptor Nomenclature, the Subcommittee recommends that the name P2Y15 should not be used when referring to this receptor

Purinergic receptor inhibition prevents the development of smoke-induced lung injury and emphisema

Extracellular ATP acts as a "danger signal" and can induce inflammation by binding to purinergic receptors. Chronic obstructive pulmonary disease is one of the most common inflammatory diseases associated with cigarette smoke inhalation, but the underlying mechanisms are incompletely understood. In this study, we show that endogenous pulmonary ATP levels are increased in a mouse model of smoke-induced acute lung inflammation and emphysema. ATP neutralization or nonspecific P2R-blockade markedly reduced smoke-induced lung inflammation and emphysema. We detected an upregulation the purinergic receptors subtypes on neutrophils (e.g., P2Y2R), macrophages, and lung tissue from animals with smoke-induced lung inflammation. By using P2Y(2)R deficient ((-/-)) animals, we show that ATP induces the recruitment of blood neutrophils to the lungs via P2Y(2)R. Moreover, P2Y(2)R deficient animals had a reduced pulmonary inflammation following acute smoke-exposure. A series of experiments with P2Y(2)R(-/-) and wild type chimera animals revealed that P2Y(2)R expression on hematopoietic cell plays the pivotal role in the observed effect. We demonstrate, for the first time, that endogenous ATP contributes to smoke-induced lung inflammation and then development of emphysema via activation of the purinergic receptor subtypes, such as P2Y(2)R