Presynaptic inhibition by adenosine A1 receptors on guinea pig small intestinal myenteric neurons.
BACKGROUND
Adenosine acts at A1 receptors to inhibit the release of most neurotransmitters. This study tested the hypothesis that both exogenous adenosine (ADO) and tonic release of endogenous ADO act at presynaptic A1 receptors to suppress excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in myenteric neurons.


METHODS
Intracellular microelectrodes were used to study actions of ADO, the agonists 2-chloro-N6-cyclopentyl ADO, its 1-deaza derivative, 5'-N-ethylcarboxamido ADO, and CGS 21680 or the antagonists 8-cyclopentyl-1,3-dimethylxanthine, its 1,3-dipropyl analog, and 1,3-dipropyl-8-p-sulfophenylxanthine on synaptic behavior in myenteric neurons.


RESULTS
Each of the agonists suppressed slow EPSPs in all 35 AH/type 2, 8 of 10 S/type 1, and 7 of 7 nonspiking neurons. ADO also decreased neuronal excitability (n = 63) in AH/type 2 neurons. Agonists suppressed fast nicotinic EPSPs in all 20 S/type 1, 10 nonspiking, and 3 AH/type 2 neurons without having any effect on postsynaptic responses to nicotinic agonists. CCPA was more potent than CGS 21680 in suppressing EPSPs. In 30% of neurons, the only action of antagonists was to block the effect of A1 or A2 agonists on EPSPs. Agonists did not inhibit IPSPs, but unmasked robust slow IPSPs by preventing slow EPSPs. Antagonists acted alone to enhance EPSPs in 70% of neurons.


CONCLUSIONS
(1) ADO acts at presynaptic A1 sites to suppress EPSPs in all neurons, (2) IPSPs are revealed by ADO, and (3) ongoing release of endogenous ADO inhibits synaptic transmission.
Christofi
F L
FL
Department of Physiology, Ohio State University, Columbus.
Wood
J D
JD
D000241:Adenosine / Q000502:physiology; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D007421:Intestine, Small / Q000294:innervation*; D009197:Myenteric Plexus / Q000166:cytology / Q000502:physiology*; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D000241:Adenosine