MacMillan, Debbi and Kennedy, Charles and McCarron, John (2012) ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors. Journal of Cell Science, 125 (21). pp. 5151-5158. ISSN 0021-9533Full text not available in this repository. (Request a copy from the Strathclyde author)
Adenosine 5′-triphosphate (ATP) mediates a variety of biological functions following nerve-evoked release, via activation of either G protein-coupled P2Y- or ligand-gated P2X-receptors. In smooth muscle, ATP, acting via P2Y receptors (P2YR), may act as an inhibitory neurotransmitter. The underlying mechanism(s) remain unclear, but have been proposed to involve the production of inositol 1,4,5-trisphosphate (IP3) by phospholipase C (PLC), to evoke Ca2+ release from the internal store and stimulation of Ca2+-activated potassium (KCa) channels to cause membrane hyperpolarization. This mechanism requires Ca2+ release from the store. However, in the present study, ATP evoked transient Ca2+ increases in only ∼10% of voltage-clamped single smooth muscle cells. These results do not support activation of KCa as the major mechanism underlying inhibition of smooth muscle activity. Interestingly, ATP inhibited IP3-evoked Ca2+ release in cells that did not show a Ca2+ rise in response to purinergic activation. The reduction in IP3-evoked Ca2+ release was not mimicked by adenosine and therefore, cannot be explained by hydrolysis of ATP to adenosine. The reduction in IP3-evoked Ca2+ release was, however, also observed with its primary metabolite, ADP, and blocked by the P2Y1R antagonist, MRS2179, and the G protein inhibitor, GDPβS, but not by PLC inhibition. The present study demonstrates a novel inhibitory effect of P2Y1R activation on IP3-evoked Ca2+ release, such that purinergic stimulation acts to prevent IP3-mediated increases in excitability in smooth muscle and promote relaxation.
|Keywords:||ATP, smooth muscle, IP3, P2Y1 receptors, Pharmacy and materia medica, Cell Biology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||08 Aug 2012 13:30|
|Last modified:||04 May 2016 22:19|