Electronic Resource
Knock-out mice reveal the contributions of P2Y and P2X receptors to nucleotide-induced Ca2+ signaling in macrophages.
| العنوان: | Knock-out mice reveal the contributions of P2Y and P2X receptors to nucleotide-induced Ca2+ signaling in macrophages. |
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| المؤلفون: | del Rey, Adriana, Renigunta, Vijay, Dalpke, Alexander H, Leipziger, J, Matos, J E, Robaye, Bernard, Zuzarte, Marylou, Kavelaars, Annemieke, Hanley, Peter J |
| المصدر: | The Journal of biological chemistry, 281 (46 |
| بيانات النشر: | 2006-11 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Immune cell function is modulated by changes in extracellular nucleotide levels. Here we used reverse transcription-PCR analyses, single cell Ca2+ imaging, and knock-out mice to define the receptors mediating nucleotide-induced Ca2+ signaling in resident peritoneal macrophages. In Ca2+-free buffer, the potent (K0.5<1 microm) stimulatory effect of UTP (or ATP) on endoplasmic reticulum (ER) Ca2+ release was abolished in cells isolated from P2Y2/P2Y4 double knock-out mice. Moreover, P2Y4(0/-), but not P2Y2-/-, macrophages responded to UTP. In P2Y2-/- macrophages, we could elicit Ca2+ responses to "pure" P2X receptor activation by applying ATP in buffer containing Ca2+. Purified UDP and ADP were ineffective agonists, although modest UDP-induced Ca2+ responses could be elicited in macrophages after "activation" with lipopolysaccharide and interferon-gamma. Notably, in Ca2+-free buffer, UTP-induced Ca2+ transients decayed within 1 min, and there was no response to repeated agonist challenge. Measurements of ER [Ca2+] with mag-fluo-4 showed that ER Ca2+ stores were depleted under these conditions. When extracellular Ca2+ was available, ER Ca2+ stores refilled, but Ca2+ increased to only approximately 40% of the initial value upon repeated UTP challenge. This apparent receptor desensitization persisted in GRK2+/- and GRK6-/- macrophages and after inhibition of candidate kinases protein kinase C and calmodulin-dependent kinase II. Initial challenge with UTP also reduced Ca2+ mobilization by complement component C5a (and vice versa). In conclusion, homologous receptor desensitization is not the major mechanism that rapidly dampens Ca2+ signaling mediated by P2Y2, the sole Gq-coupled receptor for UTP or ATP in macrophages. UDP responsiveness (P2Y6 receptor expression) increases following macrophage activation. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| مصطلحات الفهرس: | Sciences bio-médicales et agricoles, Adenosine Diphosphate -- metabolism, Animals, Calcium Channels, Calcium Signaling, Calcium-Transporting ATPases -- metabolism, G-Protein-Coupled Receptor Kinase 2, G-Protein-Coupled Receptor Kinases, Gene Expression Regulation, Macrophages, Peritoneal -- metabolism, Mice, Mice, Knockout, Nucleotides, Protein-Serine-Threonine Kinases -- genetics, Protein-Serine-Threonine Kinases -- metabolism, Receptors, Purinergic P2 -- genetics, Receptors, Purinergic P2 -- metabolism, Uridine Diphosphate -- metabolism, beta-Adrenergic Receptor Kinases -- genetics, beta-Adrenergic Receptor Kinases -- metabolism, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article |
| URL: | |
| الاتاحة: | Open access content. Open access content 1 full-text file(s): info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | 1 full-text file(s): application/pdf English |
| Other Numbers: | EQY oai:dipot.ulb.ac.be:2013/52273 uri/info:doi/10.1074/jbc.M607713200 uri/info:pii/M607713200 uri/info:pmid/16980298 uri/info:scp/33845920081 764587005 |
| المصدر المساهم: | UNIVERSITE LIBRE DE BRUXELLES From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn764587005 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |