Ta. Milner et al., Alpha(2A)-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla, BRAIN RES, 821(1), 1999, pp. 200-211
The 2A subtype of the alpha-adrenergic receptor (alpha(2A)-AR) is necessary
for the hypotensive effects of clonidine and other sympathoinhibitory adre
nergic agonists. This hypotensive response appears to be due to the inhibit
ion of sympathoexcitatory reticulospinal neurons found in the rostral ventr
olateral medulla (RVL), including neurons of the Cl adrenergic cell group.
The cellular mechanisms underlying this inhibition have not been establishe
d. Thus, this study examined the ultrastructural relationships between prof
iles containing alpha(2A)AR-immunoreactivity (alpha(2A)AR-I) and those cont
aining the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to d
etermine potential cellular substrates for alpha(2A)-AAR inhibition of Cl n
euron activity. Consistent with previous Light microscopic studies, alpha(2
A)AR-I was found in perikarya and large dendrites and the majority of these
profiles also contained TH-labeling (similar to 70% of 140). However, alph
a(2A)AR-I in these cells was primarily found within endosomes and Golgi com
plexes and in clusters associated with the endoplasmic reticula, probable s
ites for synthesis and/or trafficking of receptors. In contrast, most of th
e alpha(2A)AR-I profiles (n = 646) in the RVL were axons and axon terminals
(similar to 68%) which lacked TH immunoreactivity. alpha(2A)AR-labeled axo
ns were small and unmyelinated and labeled terminals usually formed symmetr
ic synapses an the shafts of catecholaminergic or unlabeled dendrites. Most
of these alpha(2A)AR-labeled axons were found in close proximity to TH-lab
eled profiles and approximately one-fifth (17% of 408) of the alpha(2A)AR-l
abeled axons and axon terminals directly contacted TH-labeled profiles, mos
tly dendrites. These studies suggest that alpha(2A)ARs in the Cl area of th
e RVL function primarily as heteroreceptors on presynaptic axons and termin
als of non-catecholaminergic cells, some of which provide inhibitory synapt
ic input to Cl neurons. These receptors may be activated by catecholamines
released either from the dendrites of Cl neurons or from the terminals of o
ther catecholaminergic neurons via volume transmission. (C) 1999 Elsevier S
cience B.V. All rights reserved.