Complex interactions between nitric oxide and adenosine receptors in the rat isolated nodose ganglion.
The present study has employed in vitro electrophysiology, utilising the isolated rat nodose ganglion preparation, to determine whether nitric oxide (NO) and adenosine interact with each other in vagal afferent neurons. The nucleophile NO donor, diethylamine-NO, caused reproducible, concentration-related depolarisations of the isolated rat nodose ganglia. Pre-incubation of the isolated rat nodose ganglia with the adenosine A2A receptor agonists CGS 21680 (2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride) and DPMA (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (both 1 microM) resulted in a functional antagonism of the ability of diethylamine-NO to depolarise the preparation. A similar effect was observed with adenosine (10 microM) only in the presence of the adenosine A1 receptor antagonist PACPX (1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine, 100 nM). Conversely, the adenosine A1 receptor agonists ENBA (N6-[2-endo-norbomyl]adenosine, 1 microM) and cyclohexyladenosine (100 nM) potentiated the effect of diethylamine-NO on isolated rat nodose ganglia. Inclusion of either adenosine A3 agonists or ATP had no effect on the diethylamine-NO concentration-response curve. These data suggest an ability of NO to interact, in opposing manner, with adenosine A2A and A1 receptors in rat vagal afferent neurons. On the other hand, neither A3 receptors nor ATP appear capable of interacting with NO.
Lawrence
A J
AJ
Department of Pharmacology, Monash University, Clayton, Vic., Australia. Andrew.Lawrence@med.monash.edu.au
Krstew
E
E
Jarrott
B
B
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004048:Diethylamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D009620:Nodose Ganglion / Q000187:drug effects* / Q000378:metabolism; D009636:Norbornanes / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D000970:Antineoplastic Agents; D004048:Diethylamines; C089285:N(6)-(2-endo-norbornyl)adenosine; D009636:Norbornanes; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C056426:CGS 24012; D009569:Nitric Oxide; C027513:N(6)-cyclohexyladenosine; C034281:diethylamine; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine