Alpha(2A)-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla

Citation
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
Citations number
48
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
00068993 → ACNP
Volume
821
Issue
1
Year of publication
1999
Pages
200 - 211
Database
ISI
SICI code
0006-8993(19990306)821:1<200:ARAPPH>2.0.ZU;2-E
Abstract
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.