P2X purinoceptors in the feline pulmonary vascular bed: distribution and selective in vivo pharmacological probes.
The distribution and identification of selective pharmacological probes for P2X purinoceptors in the pulmonary vascular (PV) bed of the cat have been investigated with autoradiographic and pharmacological techniques. Autoradiographic localization of the selective P2X purinoceptor ligand alpha, beta-[3H]methylene ATP (alpha, beta-MeATP) binding sites in cat lung shows that P2X purinoceptors are present in all vessels in the bed; high densities were present in large (2-mm diam) and small (0.5-mm diam) pulmonary arteries, bronchial arterioles (0.1-mm diam), and large pulmonary veins, whereas low density is characteristic of parenchymal arterioles and alveolar walls. Most of the binding is displaced with the P2X-purinoceptor agonist beta, gamma-methylene ATP and the putative selective P2X-purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) in all vessels; however, the binding is further displaced with the, P2Y-purinoceptor agonist 2-methylthio ATP (2-MeS-ATP), which suggests the presence of P2Y as well as P2X purinoceptors. P2X purinoceptors mediate potent vasoconstrictor actions in the PV bed. alpha, beta-MeATP is a selective agonist for P2X purinoceptors and does not act via serotonergic, histaminergic, adrenergic, or leukotriene vasoconstrictor receptors to produce an increase in PV resistance. The vasoconstrictor responses of alpha, beta-MeATP are attenuated by PPADS. However, PPADS has no effect on the vasodilation induced by ATP, adenosine, or 2-MeS-ATP. The diadenosine nucleotide AP5A also produced dose-dependent vasoconstrictor responses of the PV bed, which were approximately three times less potent than those of alpha, beta-MeATP and significantly reduced by PPADS. These data support that vasoconstrictor P2X purinoceptors are present on pulmonary vessels. The functional significance of these vascular P2X purinoceptors in the PV bed is not known; however, alpha, beta-MeATP, AP5A, and PPADS may be used in vivo to define their physiological role in health and disease in the lung.
Neely
C F
CF
Department of Anesthesia, Hospital of University of Pennsylvania, Philadelphia 19104, USA.
Matot
I
I
Batra
V K
VK
Bo
X
X
Burnstock
G
G
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001808:Blood Vessels / Q000378:metabolism; D002415:Cats; D011652:Pulmonary Circulation / Q000187:drug effects; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000378:metabolism*; D013268:Stimulation, Chemical; D014018:Tissue Distribution; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate