title: ATP hydrolysis pathways and their contributions to pial arteriolar dilation in rats.
abstract: ATP is thought to be released to the extracellular compartment by neurons and astrocytes during neural activation. We examined whether ATP exerts its effect of promoting pial arteriolar dilation (PAD) directly or upon conversion (via ecto-nucleotidase action) to AMP and adenosine. Blockade of extracellular direct ATP to AMP conversion, with ARL-67156, significantly reduced sciatic nerve stimulation-evoked PADs by 68%. We then monitored PADs during suffusions of ATP, ADP, AMP, and adenosine in the presence and absence of the following: 1) the ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AOPCP), 2) the A(2) receptor blocker ZM 241385, 3) the ADP P2Y(1) receptor antagonist MRS 2179, and 4) ARL-67156. Vasodilations induced by 1 and 10 μM, but not 100 μM, ATP were markedly attenuated by ZM 241385, AOPCP, and ARL-67156. Substantial loss of reactivity to 100 μM ATP required coapplications of ZM 241385 and MRS 2179. Dilations induced by ADP were blocked by MRS 2179 but were not affected by either ZM 241385 or AOPCP. AMP-elicited dilation was partially inhibited by AOPCP and completely abolished by ZM 241385. Collectively, these and previous results indicate that extracellular ATP-derived adenosine and AMP, via A(2) receptors, play key roles in neural activation-evoked PAD. However, at high extracellular ATP levels, some conversion to ADP may occur and contribute to PAD through P2Y(1) activation.
authors.affiliation: Neuroanesthesia Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vetri
authors.forename: Haoliang
authors.initials: H
authors.lastname: Xu
authors.forename: Lizhen
authors.initials: L
authors.lastname: Mao
authors.forename: Chanannait
authors.initials: C
authors.lastname: Paisansathan
authors.forename: Dale A
authors.initials: DA
authors.lastname: Pelligrino
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001160:Arterioles / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects; D012584:Sciatic Nerve / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D058917:Adenosine A2 Receptor Antagonists; D015703:Antigens, CD; D007202:Indicators and Reagents; D058921:Purinergic P2Y Receptor Antagonists; D018047:Receptors, Purinergic P1; D058472:Receptors, Purinergic P2Y1; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen