Suppression of nicotinic synaptic transmission by adenosine in myenteric ganglia of the guinea-pig gastric antrum.
Conventional intracellular recording techniques were used to investigate actions of adenosine on nicotinic cholinergic transmission in myenteric neurons of the gastric antrum. Adenosine or the more potent derivatives, 5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-cyclopropylcarboxamidoadenosine, 1-deaza-2-chloro-N6-cyclopentyladenosine or N6-cyclopentyladenosine reversibly and dose dependently inhibited the fast excitatory postsynaptic potentials (fast EPSPs) in 60% of the gastric neurons. Neither adenosine nor NECA affected excitatory responses to the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium iodine. The EC50 concentration for inhibition of the fast excitatory postsynaptic potential (EPSP) by adenosine was 55 microM NECA was a more potent inhibitor than adenosine. The specific adenosine receptor antagonists 1,3-dipropyl-8-p-sulfophenyl xanthine or 1,3-dipropyl-8-(cyclopentyl) xanthine blocked the inhibitory effects of adenosine or NECA. Fast EPSPs were enhanced by superfusion of the antagonists alone, suggestive of ongoing inhibition of nicotinic transmission by endogenous adenosine. The antagonists had no effect on resting membrane properties, excitability or antidromic action potentials. In neurons with suppression of fast EPSPs, adenosine did not suppress all cholinergic inputs to the same neuron. The results suggest that adenosine inhibits nicotinic transmission by interacting with presynaptic P1 adenosine receptors located at cholinergic release sites.
Christofi
F L
FL
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210.
Tack
J
J
Wood
J D
JD
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000502:physiology; D011706:Pyloric Antrum / Q000294:innervation; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D011978:Receptors, Nicotinic; D000241:Adenosine