Pharmacological dissection of the cellular mechanisms associated to the spontaneous and the mechanically stimulated ATP release by mesentery endothelial cells: roles of thrombin and TRPV
| Autor: | J. Pablo Huidobro-Toro, Felipe Hernández, M. Verónica Donoso, Claudio Acuña-Castillo, Tania Villalón |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Endothelium TRPV Cation Channels Stimulation Mechanotransduction Cellular TRPV Rats Sprague-Dawley Mice 03 medical and health sciences Cellular and Molecular Neuroscience Adenosine Triphosphate 0302 clinical medicine Thrombin medicine Extracellular Animals Mesentery Secretion Molecular Biology Cells Cultured Mice Knockout ATP transport Chemistry Endothelial Cells Cell Biology Adenosine Rats Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Original Article 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Purinergic Signalling. 14:121-139 |
| ISSN: | 1573-9546 1573-9538 |
| Popis: | Endothelial cells participate in extracellular ATP release elicited by mechanosensors. To characterize the dynamic interactions between mechanical and chemical factors that modulate ATP secretion by the endothelium, we assessed and compared the mechanisms participating in the spontaneous (basal) and mechanically stimulated secretion using primary cultures of rat mesentery endothelial cells. ATP/metabolites were determined in the cell media prior to (basal) and after cell media displacement or a picospritzer buffer puff used as mechanical stimuli. Mechanical stimulation increased extracellular ATP that peaked within 1 min, and decayed to basal values in 10 min. Interruption of the vesicular transport route consistently blocked the spontaneous ATP secretion. Cells maintained in media lacking external Ca2+ elicited a spontaneous rise of extracellular ATP and adenosine, but failed to elicit a further extracellular ATP secretion following mechanical stimulation. 2-APB, a TRPV agonist, increased the spontaneous ATP secretion, but reduced the mechanical stimulation-induced nucleotide release. Pannexin1 or connexin blockers and gadolinium, a Piezo1 blocker, reduced the mechanically induced ATP release without altering spontaneous nucleotide levels. Moreover, thrombin or related agonists increased extracellular ATP secretion elicited by mechanical stimulation, without modifying spontaneous release. In sum, present results allow inferring that the spontaneous, extracellular nucleotide secretion is essentially mediated by ATP containing vesicles, while the mechanically induced secretion occurs essentially by connexin or pannexin1 hemichannel ATP transport, a finding fully supported by results from Panx1−/− rodents. Only the latter component is modulated by thrombin and related receptor agonists, highlighting a novel endothelium-smooth muscle signaling role of this anticoagulant. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink