title: P2-purinoceptors mediate both vasodilation (via the endothelium) and vasoconstriction of the isolated rat femoral artery.
abstract: The distribution of P1- and P2-purinoceptors in isolated rat femoral artery was studied by comparing responses to ATP, alpha, beta-methylene ATP and adenosine, both when endothelial cells were intact and when they had been removed by mechanical rubbing (as confirmed by histochemical staining and abolition of relaxations to acetylcholine). alpha, beta-Methylene ATP and ATP (but not adenosine or acetylcholine) contracted preparations at resting tone. alpha, beta-Methylene ATP was significantly more potent than ATP. The potency of both alpha, beta-methylene ATP and ATP was significantly increased in the absence of the endothelium. These contractions were unaffected by tetrodotoxin, phentolamine and methysergide in concentrations sufficient to abolish contractions to perivascular nerve stimulation, noradrenaline or 5-hydroxytryptamine. Acetylcholine, ATP and adenosine relaxed arteries whose tone had been raised by 10(-6) M noradrenaline. Removal of the endothelium abolished relaxations to ATP (contractions were seen instead) and acetylcholine, but not to adenosine. alpha, beta-Methylene ATP further contracted the high tone preparation and was again more potent when the endothelium was absent. ATP and alpha, beta-methylene ATP were more potent as contractile agents when noradrenaline was present. These results confirm that endothelial cells can mediate vasodilation. They also show that ATP can act at P2-purinoceptors at two locations in the isolated rat femoral artery; one on the endothelium leading to vasodilation, and the other on the smooth muscle leading to vasoconstriction. P1-Purinoceptors, however, appear to be located on the smooth muscle only and mediate vasodilation. At the smooth muscle P2-purinoceptor, alpha, beta-methylene ATP is more potent than ATP, whereas at the endothelial P2-purinoceptor, the reverse is true.
authors.forename: C
authors.initials: C
authors.lastname: Kennedy
authors.forename: D
authors.initials: D
authors.lastname: Delbro
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004727:Endothelium / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011983:Receptors, Purinergic; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine