Alpha2A-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla.

The 2A subtype of the alpha-adrenergic receptor (alpha2A-AR) is necessary for the hypotensive effects of clonidine and other sympathoinhibitory adrenergic agonists. This hypotensive response appears to be due to the inhibition of sympathoexcitatory reticulospinal neurons found in the rostral ventrolateral medulla (RVL), including neurons of the C1 adrenergic cell group. The cellular mechanisms underlying this inhibition have not been established. Thus, this study examined the ultrastructural relationships between profiles containing alpha2AAR-immunoreactivity (alpha2AAR-I) and those containing the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to determine potential cellular substrates for alpha2A-AR inhibition of C1 neuron activity. Consistent with previous light microscopic studies, alpha2AAR-I was found in perikarya and large dendrites and the majority of these profiles also contained TH-labeling (approximately 70% of 140). However, alpha2AAR-I in these cells was primarily found within endosomes and Golgi complexes and in clusters associated with the endoplasmic reticula, probable sites for synthesis and/or trafficking of receptors. In contrast, most of the alpha2AAR-I profiles (n=646) in the RVL were axons and axon terminals (approximately 68%) which lacked TH immunoreactivity. alpha2AAR-labeled axons were small and unmyelinated and labeled terminals usually formed symmetric synapses on the shafts of catecholaminergic or unlabeled dendrites. Most of these alpha2AAR-labeled axons were found in close proximity to TH-labeled profiles and approximately one-fifth (17% of 408) of the alpha2AAR-labeled axons and axon terminals directly contacted TH-labeled profiles, mostly dendrites. These studies suggest that alpha2AARs in the C1 area of the RVL function primarily as heteroreceptors on presynaptic axons and terminals of non-catecholaminergic cells, some of which provide inhibitory synaptic input to C1 neurons. These receptors may be activated by catecholamines released either from the dendrites of C1 neurons or from the terminals of other catecholaminergic neurons via volume transmission.