Neuronal release of soluble nucleotidases and their role in neurotransmitter inactivation.
Efficient control of synaptic transmission requires a rapid mechanism for terminating the actions of neurotransmitters. For amino acids and monoamines, this is achieved by their uptake into the cell by specific high-affinity transporters; acetylcholine is first broken down in the extracellular space and then choline is taken up by the cell. Because ATP is hydrolysed to adenosine by membrane-bound enzymes (ectonucleotidases) that are present in most tissues, it has been assumed that these enzymes terminate the neurotransmitter actions of ATP in the brain and in the periphery. We show here, however, that stimulation of sympathetic nerves innervating the guinea-pig vas deferens releases not only neuronal ATP, but also soluble nucleotidases that break down this ATP to adenosine, indicating that inactivation of ATP is increased by nerve activity. This release of specific nucleotidases together with ATP represents a new mechanism for terminating the actions of a neurotransmitter.
Todorov
L D
LD
Department of Pharmacology, University of Nevada School of Medicine, Reno 89557, USA.
Mihaylova-Todorova
S
S
Westfall
T D
TD
Sneddon
P
P
Kennedy
C
C
Bjur
R A
RA
Westfall
D P
DP
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004985:Ethenoadenosine Triphosphate / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009708:Nucleotidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012995:Solubility; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism; D014649:Vas Deferens / Q000294:innervation / Q000378:metabolism
C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; D004985:Ethenoadenosine Triphosphate; D018377:Neurotransmitter Agents; D000255:Adenosine Triphosphate; D009708:Nucleotidases; D002118:Calcium; D009638:Norepinephrine