Adenosine A1 receptors are located predominantly on axons in the rat hippocampal formation

Abstract

The nucleoside adenosine exerts potent biological effects via specific receptors, including the inhibitory A1 adenosine receptor (A1AR). In the hippocampus A1ARs play an important role in regulating neuronal activity. However, the cellular sites of hippocampal A1ARs are undefined. Using in situ hybridization, receptor autoradiography, and single- and double-label immunocytochemistry techniques, we have characterized the cellular sites of A1AR expression in the rat hippocampus. In situ hybridization and receptor autoradiography studies revealed strikingly different patterns of labeling. In situ hybridization studies revealed heaviest labeling of cell bodies in the granular layer of the dentate gyrus and the pyramidal layers of Ammon's horn. In contrast, using [3H]DPCPX, we observed heavy specific labeling over the neuropil in the dentate hilus stratum moleculare, stratum lacunosum-moleculare, stratum radiatum, and stratum oriens, and little labeling over cell bodies. Using single-label immunocytochemistry, A1AR immunoreactivity was found to be heaviest over fibers in regions corresponding with heavy [3H]DPCPX labeling. Double-label florescent confocal microscopy was then used to determine the identity of labeled fibers. A1AR immunoreactivity was found to co-localize with SMI-31 that labels axons, but not with MAP2a,b that labels cell bodies and dendrites, or with synaptophysin that labels synapses. These data identify axons as the predominant site of A1AR expression in hippocampus. Activation of A1ARs may be a powerful mechanism by which adenosine alters axonal transmission to inhibit neurotransmitter release.

Long-Term Potentiation Is Impaired in Middle-Aged Rats: Regional Specificity and Reversal by Adenosine Receptor Antagonists

“…Some differentiation was apparent within these areas and, in particular, immunostaining was less dense in the apical dendritic layers of CA3 and dentate gyrus than it was in the dendritic fields of CA1. These results are in general agreement with previous studies of ligand binding (Lee et al, 1986;Swanson et al, 1995;Shearman and Weaver, 1997) and, in fewer instances, immunostaining Swanson et al, 1995) for adenosine A 1 Rs.…”

Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection

“…Now, we extended these findings to neurons, the brain cells where the predominant expression of adenosine A 1 receptors occurs (Onodera and Kogure, 1988;Ulas et al, 1993;Swanson et al, 1995) and where adenosine acts to refrain excitatory transmission and to protect from uncoordinated firing (Dragunow, 1988;Dunwiddie and Masino, 2001). Indeed, the neuronal adenosine A 1 receptor represents a major endogenous neuroprotective system and it has long been suggested that the upregulation of A 1 receptor expression increases its IL-6, neuronal adenosine A 1 receptor and brain function K Biber et al neuroprotective capacities (for review, see Rudolphi and Schubert, 1996;Dunwiddie and Masino, 2001).…”

Adenosine Postsynaptically Modulates Supraoptic Neuronal Excitability

“…In support of this are studies showing the location and physiological activation of A 1 receptors on axons (Swanson et al 1995(Swanson et al , 1998 along with earlier studies directly monitoring the effect of adenosine on the spike afterhyperpolarization (Haas and Greene 1984). However, the Ca 2ϩ spike-generated I AHP seen in the presence of TTX and TEA was not enhanced by adenosine in either amplitude or duration.…”