S. Mihaylova-todorova et al., Correlation between the release of the sympathetic neurotransmitter ATP and soluble nucleotidases from the guinea pig vas deferens, J PHARM EXP, 296(1), 2001, pp. 64-70
Citations number
18
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Recently, we have shown that by releasing specific nucleotidases the sympat
hetic nerves of the guinea pig vas deferens may regulate the metabolism of
extracellular adenine nucleotides and consequently, the inactivation of neu
rotransmitter ATP. Based on the evidence for tetrodotoxin sensitivity and c
alcium dependence of the nerve stimulation-evoked overflow of enzyme activi
ty, we have suggested that soluble nucleotidases may be stored in synaptic
vesicles within the sympathetic nerves and released upon arrival of nerve a
ction potentials by a mechanism similar to that for release of neurotransmi
tters. To further test this hypothesis we studied the time course of nerve
stimulation-evoked overflow of ATP, norepinephrine (NE), releasable ATPase
(r-ATPase) activity, and releasable AMPase (r-AMPase) activity under contro
l conditions and in the presence of drugs known to selectively modulate sym
pathetic neurotransmission. The results show that the time course of overfl
ow of r-ATPase and r-AMPase activities resembles the transient pattern of o
verflow of ATP but not the tonic pattern of overflow of NE. Vasa deferentia
dissected from animals treated with reserpine release ATP, r-ATPase, and r
-AMPase, whereas the overflow of NE is completely abolished. Guanethidine,
on the other hand, inhibits equally well the overflow of the two neurotrans
mitters and the releasable nucleotidase activities. Agonists of the alpha (
2)-adrenergic receptors abolish the overflow of ATP, r-ATPase, and r-AMPase
but not the overflow of NE. This evidence supports the idea that the sympa
thetic nerves of the guinea pig vas deferens store and release ATP together
with specific nucleotidases responsible for the inactivation of this neuro
transmitter.