Complex interactions between nitric oxide and adenosine receptors in the rat isolated nodose ganglion

Abstract

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 A 2A receptor agonists CGS 21680 (2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine hydrochloride) and DPMA ( N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (both 1 μM) resulted in a functional antagonism of the ability of diethylamine-NO to depolarise the preparation. A similar effect was observed with adenosine (10 μM) only in the presence of the adenosine A 1 receptor antagonist PACPX (1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine, 100 nM). Conversely, the adenosine A 1 receptor agonists ENBA ( N 6-[2-endo-norbornyl]adenosine, 1 μM) and cyclohexyladenosine (100 nM) potentiated the effect of diethylamine-NO on isolated rat nodose ganglia. Inclusion of either adenosine A 3 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 A 2A and A 1 receptors in rat vagal afferent neurons. On the other hand, neither A 3 receptors nor ATP appear capable of interacting with NO.