Presynaptic adenosine A2a receptors on soma and central terminals of rat vagal afferent neurons.
The dorsal vagal complex of the medulla oblongata is a key centre involved in the regulation of numerous autonomic functions, including cardiovascular control. Adenosine has been implicated as a potential neuromodulator of the baroreceptor reflex, and therefore the current study has investigated the presence and characteristics of adenosine receptors on rat vagal afferent neurons. In the nodose-vagal grease gap preparation, the adenosine A2a agonist CGS-21680 evoked a depolarisation only in the presence of the selective adenosine A1 antagonist PACPX. Autoradiography using [3H]NECA (4 nM) with suppression of A1 binding enabled the first visualisation of high affinity adenosine A2 receptors in the nucleus tractus solitarius (NTS). Unilateral nodose ganglionectomy resulted in over 90% reduction in binding in the lesioned (ipsilateral) NTS compared to a sham control. Furthermore, local administration of CGS-21680 increased evoked glutamate release in the NTS, as measured by in vivo microdialysis. These data suggest the presence of presynaptic adenosine A2a receptors on both the soma and central terminals of rat vagal afferent neurons, and thereby support the hypothesis that adenosine may have a modulatory role in the baroreceptor reflex.
Department of Pharmacology, Monash University, Clayton, Vic., Australia.
M
M
Castillo-Meléndez
E
E
Krstew
A J
AJ
Lawrence
B
B
Jarrott
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001345:Autoradiography; D001933:Brain Stem / Q000033:anatomy & histology / Q000378:metabolism; D004594:Electrophysiology; D015171:Ganglionectomy; D008297:Male; D017551:Microdialysis; D009411:Nerve Endings / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D017552:Solitary Nucleus / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D000596:Amino Acids; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D010627:Phenethylamines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine