Biology Reference
In-Depth Information
non-junctional channels that play paracrine roles by releasing ATP [110, 96,
104, 95].
While ATP can be released into the extracellular space, it is not the only puriner-
gic nucleotide that can be present in the extracellular medium after stimulation of
cells. ATP can be hydrolyzed by ecto-nucleotidases to ADP, AMP and adenosine
(for review see [128]). Ecto-nucleotidases belong to different subfamilies. E-NPPs
hydrolyze ATP to AMP, E-NTPDases can hydrolyze ATP to ADP and ADP to AMP,
while ecto-5
nucleotidase converts AMP to adenosine. Adenosine can be further
converted to inosine by adenosine deaminase. The ecto-nucleotidases are impor-
tant for the relation of purinergic IC. Since they regulate the local levels of the
nucleotides, they can influence the magnitude and duration of purinergic signaling,
and because of the presence of different nucleotide receptors on the extracellular
surface of the membranes, they can affect the type of response of cells to purinergic
signaling [65].
The purinergic messengers involved in IC can act on a large variety of recep-
tors belonging to two main families: P1 or adenosine receptors, and P2 receptors
for which ATP (or ADP) are physiological agonists. The P1 receptor family is fur-
ther subdivided into four subtypes: A1, A2A, A2B and A3. All adenosine receptors
have seven putative transmembrane domains with an extracellular N-terminus and
a cytoplasmic C-terminus, and they couple to G proteins. The A2A and A2B recep-
tors preferably interact with members of the Gs family of G proteins, stimulating
adenylyl cyclase, and the A1 and A3 receptors interact with Gi/o proteins, inhibiting
adenylyl cyclase.
The P2 receptors are divided into ionotropic P2X and metabotropic (G protein-
coupled) P2Y receptors, respectively. Mammalian P2X receptors belong to a family
of at least seven proteins (P2X1-P2X7) of ligand-gated ion channels, which allow
Ca
2+
influx from the extracellular space upon activation. P2Y receptors form a
large subfamily of purine and pyrimidine nucleotide receptors that are coupled to
G proteins. They stimulate a release of intracellular Ca
2+
from stores through phos-
pholipase C (PLC)-mediated PIP
2
hydrolysis and activation of the IP
3
pathway.
There are at least eight subtypes of P2Y receptors, namely P2Y1, P2Y2, P2Y4,
P2Y6, P2Y11, P2Y12, P2Y13 and P2Y14, but purine nucleotides are full agonists
only for P2Y1, P2Y2, P2Y11, P2Y12 and P2Y13. P2Y1 and P2Y12 receptors are
preferentially activated by ADP, P2Y2 and P2Y4 by UTP, P2Y6 by UDP, and P2Y2
and P2Y11 are mainly activated by ATP (IUPHAR Database).
10.2 AIM
In several cell types, IC is mediated by both GJIC and purinergic PIC. Corneal
endothelial cells contain gap junctions and also express purinergic receptors. It is,
therefore, likely that both types of IC could be present in the corneal endothe-
lial monolayer, and play a role in homeostasis and in the coordination of cellular
activity. The importance of GJIC and PIC in normal conditions and in response
Search WWH ::
Custom Search