Autoradiographic visualisation of axonal transport of adenosine A1 receptors along the rat vagus nerve and characterisation of adenosine A1 receptor binding in the dorsal vagal complex of hypertensive and normotensive rats.
The present study had employed in vitro receptor autoradiography with [3H]DPCPX to visualise the presence of adenosine A1 receptors on the rat nodose ganglion, which contains the perikarya of vagal afferent neurons projecting the the nucleus tractus solitarius (NTS). In addition, unilateral vagal ligation resulted in an accumulation of [3H]DPCPX binding adjacent to the ligatures, indication that adenosine A1 receptors are subject to axoplasmic flow along the rat vagus nerve. Radioligand binding assays were utilised to characterise the properties of adenosine A1 receptors in the dorsal vagal complex (NTS, area postrema and dorsal motor nucleus of the vagus) of pup and adult normotensive (Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensive, SHR) rats. Saturation binding indicated that the affinity (KD) of [3H]DPCPX, and the binding site density (Bmax) were not different between the adult WKY and SHR, although the pup SHR had a lower KD value than the pup WKY rat. Competition binding assays revealed complex differences between the two rat strains; however, with respect to hypertension, the affinity of the selective adenosine A1 agonist, cyclohexyladenosine (CHA), was markedly reduced in the membranes from SHR (Ki approximately 93 nM) compared to WKY (approximately 6 nM). Such an observation is consistent with the attenuated responses of SHRs to intra-NTS injections of adenosine.
Krstew
E
E
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Jarrott
B
B
Lawrence
A J
AJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001370:Axonal Transport / Q000502:physiology*; D001667:Binding, Competitive; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012016:Reference Values; D017552:Solitary Nucleus / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine