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Cellular mechanisms underlying the excitatory actions of ATP in vascular smooth muscle
Author(s) -
Kennedy Charles
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280343
Subject(s) - excitatory postsynaptic potential , suramin , stimulation , adenosine , neurotransmission , adenosine triphosphate , vascular smooth muscle , chemistry , purinergic receptor , biophysics , muscle contraction , endocrinology , neuropeptide y receptor , medicine , biology , neuroscience , neuropeptide , biochemistry , inhibitory postsynaptic potential , receptor , smooth muscle
It is now clear that noradrenaline (NA) is not the sole excitatory cotransmitter in perivascular sympathetic nerves, as both adenosine 5′‐triphosphate (ATP) and neuropeptide Y (NPY) are co‐stored with NA in synaptic vesicles and co‐released during nerve stimulation. The relative contribution of these compounds to neurogenic contractions is dependent upon the species, vessel and parameters of stimulation studied. Stimulation of the perivascular nerves evokes excitatory junction potentials (ejps) which, in most vessels are resistant to α‐adrenoceptor antagonists. The ejps are mediated by ATP, as they are selectively abolished by desensitisation of the P 2x ‐purinoceptor by α,β‐MeATP or by the selective P 2 ‐antagonist, suramin. In many vessels a component of the neurogenic contraction also shows resistance to β‐adrenoceptor blockade but can be inhibited by α,β‐MeATP or suramin. In the limited number of vessels studied to date, ATP has been found to act via several ionic mechanisms, including an increasing in a non‐specific, cationic current and an increase in a chloride current. These currents appear to have a variable distribution and are not all present in all vessels. This may allow vessels a differential response to ATP depending on their function. However, the distribution, role and relative importance of these effects is not yet known. As well as its direct contractile effects, ATP also interacts in a synergistic manner with NA and NPY. The mechanisms which underlie these effects are unclear but may involve an increase in the current through L‐type calcium channels. Clearly, vascular neurotransmission is not the simple process previously envisaged. © 1993 Wiley‐Liss, Inc.