Activation of presynaptic A1-receptors by endogenous adenosine inhibits acetylcholine release in the guinea-pig ileum.
1. It is well established that presynaptic adenosine A1-receptor activation inhibits acetylcholine (ACh) release in the guinea-pig ileum. The present study extends this observation and examines a possible role for endogenous adenosine in modulating cholinergic nerve function. 2. The actions of the adenosine uptake blocker, dipyridamole, the adenosine deaminase inhibitor, erythro-9(2-hydroxy-3-nonyl)adenine (EHNA) and the A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) were examined on electrically evoked neurogenic, cholinergic twitch contractions of the guinea-pig ileum. Some additional studies measuring [3H]-ACh release were also performed. 3. Adenosine and the selective A1-receptor agonist, 2-chloroadenosine (2-CA), inhibited electrically evoked contractions and, in the case of 2-CA, [3H]-ACh release. The actions were antagonized by DPCPX. At low concentrations, dipyridamole and EHNA enhanced the effect of adenosine causing a leftward shift of the concentration-response curve. In contrast, inhibition induced by 2-CA was unaffected by either dipyridamole or EHNA. 4. When applied alone at higher concentrations, EHNA and dipyridamole produced a concentration-dependent suppression of cholinergic neurotransmission. In both cases, the effect could be reversed by DPCPX. At the same concentration, DPCPX alone produced a small but consistent increase in twitch height and [3H]-ACh release. 5. The data confirm the existence of inhibitory presynaptic adenosine A1-receptors modulating cholinergic nerve function in the guinea-pig ileum and suggests that these receptors can be activated by endogenous adenosine released either as adenosine itself or as an ATP metabolite.
Lee
J J
JJ
Biosciences Division, University of Hertfordshire, College Lane, Hatfield, Hertfordshire, UK.
Talubmook
C
C
Parsons
M E
ME
D000109:Acetylcholine / Q000378:metabolism*; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002799:Cholinergic Fibers / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D014970:Xanthines; C010192:9-(2-hydroxy-3-nonyl)adenine; D004176:Dipyridamole; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000243:Adenosine Deaminase; D000225:Adenine; D000241:Adenosine; D000109:Acetylcholine