ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors
| Autor: | D, MacMillan, C, Kennedy, J G, McCarron |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Patch-Clamp Techniques Colon Guinea Pigs Myocytes Smooth Muscle Inositol 1 4 5-Trisphosphate In Vitro Techniques Guanosine Diphosphate Article Receptors Purinergic P2Y1 Adenosine Triphosphate Smooth muscle Animals Inositol 1 4 5-Trisphosphate Receptors Calcium Signaling Phospholipid Ethers Ryanodine Receptor Calcium Release Channel Thionucleotides Adenosine Diphosphate ATP Calcium Channel Agonists Sarcoplasmic Reticulum Type C Phospholipases Ins(1 4 5)P3 Purinergic P2Y Receptor Antagonists Carbachol Calcium Purinergic P2Y Receptor Agonists |
| Zdroj: | Journal of cell science |
| ISSN: | 1477-9137 |
| Popis: | 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 [Ins(1,4,5)P(3)] by phospholipase C (PLC), to evoke Ca(2+) release from the internal store and stimulation of Ca(2+)-activated potassium (K(Ca)) channels to cause membrane hyperpolarization. This mechanism requires Ca(2+) release from the store. However, in the present study, ATP evoked transient Ca(2+) increases in only ∼10% of voltage-clamped single smooth muscle cells. These results do not support activation of K(Ca) as the major mechanism underlying inhibition of smooth muscle activity. Interestingly, ATP inhibited Ins(1,4,5)P(3)-evoked Ca(2+) release in cells that did not show a Ca(2+) rise in response to purinergic activation. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was not mimicked by adenosine and therefore, cannot be explained by hydrolysis of ATP to adenosine. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was, however, also observed with its primary metabolite, ADP, and blocked by the P2Y(1)R antagonist, MRS2179, and the G protein inhibitor, GDPβS, but not by PLC inhibition. The present study demonstrates a novel inhibitory effect of P2Y(1)R activation on Ins(1,4,5)P(3)-evoked Ca(2+) release, such that purinergic stimulation acts to prevent Ins(1,4,5)P(3)-mediated increases in excitability in smooth muscle and promote relaxation. |
| Databáze: | OpenAIRE |
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