Vessel Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 372

Tabl e 7. 9. Nucleoside and nucleotide receptors (Sources: [ 691 , 692 ]).

Ligand Receptors

Nucleoside

Adenosine A 1 ,A 2 A A 2 B ,A 3

Purine nucleotides

AT P P 2 X 1 ,P2X 7 ,

P2Y 1 ,P2Y 2 ,P2Y 4 ,P2Y 11

ADP P2Y 1 ,P2Y 12 ,P2Y 13

Pyrimidine nucleotides

UTP P2Y 2 ,P2Y 4

UDP P2Y 6 ,P2Y 14

UDP glucose

P2Y 14

7.9.2 Nucleotide Receptors

Purinergic (nucleoside and nucleotide) receptors include G-protein-coupled P1 re-
ceptors that bind the nucleoside adenosine (A 1 ,A 2A ,A 2B ,andA 3 ) and P2 receptors,
either ionotropic P2X (ligand-gated ion channels P2X 1 -P2X 7 ) or metabotropic P2Y
receptors (G-protein-coupled receptors P2Y 1 -P2Y 2 ,P2Y 4 ,P2Y 6 ,andP2Y 11 -
P2Y 14 ;Table 7.9 ).
Activation of P2X receptor channel by ATP triggers the influx of extracellular
cations, such as Na + and Ca 2 + ions. The subsequent cell depolarization can excite
voltage-gated channels. Activation of G-protein-coupled P2Y receptors can provoke
changes in concentrations of intracellular cAMP or Ca 2 + messengers via the Gs-
ACase, Gq-PLC, and Gi-ion channel pathways.
Entry of Ca 2 + ions through P2X 1 receptors in vascular smooth myocytes causes
vasoconstriction. On the other hand, release of Ca 2 + ions from the endoplasmic
reticulum triggered by P2Y 1 and P2Y 2 receptors in vascular endothelial cells results
from the production of inositol triphosphate that stimulates IP 3 receptors; it elicits
activation of endothelial nitric oxide synthase NOS3, thereby synthesizing the
gasotransmitter nitric oxide that induces vasodilation. Similarly, activation of P2X
receptors on the endothelial cell surface leads to vasodilation; excitation of P2Y
receptors on the smooth myocyte surface causes vasoconstriction.

7.9.3 ATP Release

Release of ATP and other nucleotides by non-excitable cells occurs in 3 circum-
stances: (1) upon mechanical stresses sensed by endothelial and smooth muscle
cells among others; (2) following chemical stimuli; and (3) in resting cells.
Mediator ATP is liberated out of vascular cells (vascular endothelial and smooth