ATP: a vasoactive signal in the pericyte-containing microvasculature of the rat retina.
In this study we tested the hypothesis that extracellular ATP regulates the function of the pericyte-containing retinal microvessels. Pericytes, which are more numerous in the retina than in any other tissue, are abluminally located cells that may adjust capillary perfusion by contracting and relaxing. At present, knowledge of the vasoactive molecules that regulate pericyte function is limited. Here, we focused on the actions of extracellular ATP because this nucleotide is a putative glial-to-vascular signal, as well as being a substance released by activated platelets and injured cells. In microvessels freshly isolated from the adult rat retina, we monitored ionic currents via perforated-patch pipettes, measured intracellular calcium levels with the use of fura-2, and visualized microvascular contractions with the aid of time-lapse photography. We found that ATP induced depolarizing changes in the ionic currents, increased calcium levels and caused pericytes to contract. P2X7 receptors and UTP-activated receptors mediated these effects. Consistent with ATP serving as a vasoconstrictor for the pericyte-containing microvasculature of the retina, the microvascular lumen narrowed when an adjacent pericyte contracted. In addition, the sustained activation of P2X7 receptors inhibited cell-to-cell electrotonic transmission within the microvascular networks. Thus, ATP not only affects the contractility of individual pericytes, but also appears to regulate the spatial and temporal dynamics of the vasomotor response.
Kawamura
Hajime
H
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor 48105, USA.
Sugiyama
Tetsuya
T
Wu
David M
DM
Kobayashi
Masato
M
Yamanishi
Shigeki
S
Katsumura
Kozo
K
Puro
Donald G
DG
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D020286:Pericytes / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058486:Receptors, Purinergic P2X7; D012160:Retina / Q000502:physiology*; D012171:Retinal Vessels / Q000166:cytology / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology
C546470:P2rx7 protein, rat; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D014544:Uridine Triphosphate