Highlights
- •Structural biology and sympathetic co-transmission
- •Role of P2X1 receptors in vas deferens co-transmission
- •Structure of P2X receptors based on zfP2X4 receptor crystals
- •Structural views of ATP receptors, ectonucleotidases and transporters
- •Sympathetic co-transmission and lipid rafts
Abstract
The vas deferens is a simple bioassay widely used to study the physiology of sympathetic
neurotransmission and the pharmacodynamics of adrenergic drugs. The role of ATP as
a sympathetic co-transmitter has gained increasing attention and furthered our understanding
of its role in sympathetic reflexes. In addition, new information has emerged on the
mechanisms underlying the storage and release of ATP. Both noradrenaline and ATP concur
to elicit the tissue smooth muscle contractions following sympathetic reflexes or
electrical field stimulation of the sympathetic nerve terminals. ATP and adenosine
(its metabolic byproduct) are powerful presynaptic regulators of co-transmitter actions.
In addition, neuropeptide Y, the third member of the sympathetic triad, is an endogenous
modulator. The peptide plus ATP and/or adenosine play a significant role as sympathetic
modulators of transmitter's release. This review focuses on the physiological principles
that govern sympathetic co-transmitter activity, with special interest in defining
the motor role of ATP. In addition, we intended to review the recent structural biology
findings related to the topology of the P2X1R based on the crystallized P2X4 receptor
from Danio rerio, or the crystallized adenosine A2A receptor as a member of the G protein coupled
family of receptors as prototype neuro modulators. This review also covers structural
elements of ectonucleotidases, since some members are found in the vas deferens neuro-effector
junction. The allosteric principles that apply to purinoceptors are also reviewed
highlighting concepts derived from receptor theory at the light of the current available
structural elements. Finally, we discuss clinical applications of these concepts.
Keywords
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Article info
Publication history
Published online: May 31, 2014
Accepted:
May 20,
2014
Received in revised form:
May 14,
2014
Received:
November 27,
2013
Identification
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© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
