Role of extracellular UTP in the release of uracil from vasoconstricted hindlimb.
The source and function of elevated uracil release during vasoconstriction in the perfused rat hindlimb was investigated. The possibility that uracil release derived from the breakdown of released vasoactive uridine 5'-triphosphate (UTP) was examined. Exogenous UTP was found to be a potent vasodilator in the perfused rat hindlimb, opposing norepinephrine and angiotensin-induced increases in vasoconstriction and oxygen consumption. UTP was rapidly catabolized by the hindlimb to uridine 5'-monophosphate (UMP), uridine, and uracil, which were all devoid of vasoactivity. UTP was similarly catabolized by incubated rat aorta. Degradation of exogenous UTP by perfused hindlimb or aorta was inhibited by alpha, beta-methylene-adenosine 5'-diphosphate (AMP-CP), an inhibitor of ectonucleotidases. However, AMP-CP did not decrease uracil and uridine output by the hindlimb during angiotensin-mediated vasoconstriction and increased oxygen consumption. In particular, simultaneous infusion of AMP-CP with angiotensin did not increase efflux of UMP. Although exogenous UTP is a potent vasodilator in the perfused rat hindlimb, it appears not to be released intact during vasoconstriction. Hence, extracellular UTP is unlikely to be the precursor of the uracil release.
Richards
S M
SM
Department of Biochemistry, University of Tasmania, Hobart, Australia.
Dora
K A
KA
Rattigan
S
S
Colquhoun
E Q
EQ
Clark
M G
MG
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014498:Uracil / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D014661:Vasoconstriction
D009711:Nucleotides; C045716:adenosine 2',5'-diphosphate; D014498:Uracil; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014542:Uridine Monophosphate; D014544:Uridine Triphosphate