Autoradiographic visualisation of axonal transport of adenosine A 1 receptors along the rat vagus nerve and characterisation of adenosine A 1 receptor binding in the dorsal vagal complex of hypertensive and normotensive rats

Abstract

The present study has employed in vitro receptor autoradiography with [ 3 H ]DPCPX to visualise the presence of adenosine A 1 receptors on the rat nodose ganglion, which contains the perikarya of vagal afferent neurons projecting to the nucleus tractus solitarius (NTS). In addition, unilateral vagal ligation resulted in an accumulation of [ 3 H ]DPCPX binding adjacent to the ligatures, indicating that adenosine A 1 receptors are subject to axoplasmic flow along the rat vagus nerve. Radioligand binding assays were utilised to characterise the properties of adenosine A 1 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 ( K D) of [ 3 H ]DPCPX, and the binding site density ( B max) were not different between the adult WKY and SHR, although the pup SHR had a lower K D 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 A 1 agonist, cyclohexyladenosine (CHA), was markedly reduced in the membranes from SHR ( K i∼93 nM) compared to WKY (∼6 nM). Such an observation is consistent with the attenuated responses of SHRs to intra-NTS injections of adenosine.