Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine.
Slices of rabbit hippocampus were preincubated with [3H]serotonin then superfused continuously and stimulated twice electrically. The stimulation-evoked overflow of tritium was Ca2+-dependent, tetrodotoxin-sensitive and subject to modulation by serotonin autoreceptors. It was decreased by various adenosine receptor agonists in an order of potency that was typical for A1-(Ri-) receptors: N6-cyclohexyladenosine greater than (-)N6-phenylisopropyladenosine greater than 5'-N-ethylcarboxamideadenosine greater than (+)N6-phenylisopropyladenosine = adenosine. The effects of the agonists were antagonized by 8-phenyltheophylline. The hypothesis that endogenous adenosine influences hippocampal serotonin release is supported by the following findings: both the adenosine receptor antagonists (theophylline or 8-phenyltheophylline (10 microM, each)) and the enzyme adenosine deaminase (10 micrograms/ml) increased, whereas R-E 244 (3 microM), an inhibitor of adenosine uptake, significantly decreased the evoked tritium overflow. When 8-phenyltheophylline was present throughout superfusion the effects of both R-E 244 and exogenous adenosine deaminase were abolished. It is concluded that serotonin release in the rabbit hippocampus is depressed by endogenous adenosine via A1-(Ri-) receptors.
Feuerstein
T J
TJ
Hertting
G
G
Jackisch
R
R
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D013779:Tetrodotoxin; D000243:Adenosine Deaminase; D000241:Adenosine