TY - JOUR
T1 - Alpha(2A)-adrenergic receptors are primarily presynaptic heteroreceptors in the C1 area of the rat rostral ventrolateral medulla
AU - Milner, Teresa A.
AU - Rosin, Diane L.
AU - Lee, Amy
AU - Aicher, Sue A.
N1 - Funding Information:
We would like to thank Dr. Patrice Guyenet for his helpful suggestions on the manuscript. We also thank Dr. Kevin R. Lynch for generously suppling the antibodies to α 2A ARs and Ms. Sabrina Prince, Sarita Sharma and Zina Capiello for technical assistance. Grant support: NIH grants HL18974 (T.A.M. and S.A.A.) and F31MH11074 (A.L.), Scottish Rite Schizo. Res. Prog. and Tourette Syndrome Permanent Research Fund (D.L.R.), AHA 95011200 (K.R.L.) and American Heart Association Established Investigator Award (S.A.A.).
PY - 1999/3/6
Y1 - 1999/3/6
N2 - The 2A subtype of the alpha-adrenergic receptor (α(2A)-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 α(2A) AR-immunoreactivity (α(2A) AR-I) and those containing the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to determine potential cellular substrates for α(2A)-AR inhibition of C1 neuron activity. Consistent with previous light microscopic studies, α(2A) AR-I was found in perikarya and large dendrites and the majority of these profiles also contained TH-labeling (~ 70% of 140). However, α(2A) AR-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 α(2A) AR-I profiles (n = 646) in the RVL were axons and axon terminals (~ 68%) which lacked TH immunoreactivity, α(2A) AR-labeled axons were small and unmyelinated and labeled terminals usually formed symmetric synapses on the shafts of catecholaminergic or unlabeled dendrites. Most of these α(2A) AR- labeled axons were found in close proximity to TH-labeled profiles and approximately one-fifth (17% of 408) of the α(2A) AR-labeled axons and axon terminals directly contacted TH-labeled profiles, mostly dendrites. These studies suggest that α(2A) ARs 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.
AB - The 2A subtype of the alpha-adrenergic receptor (α(2A)-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 α(2A) AR-immunoreactivity (α(2A) AR-I) and those containing the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) to determine potential cellular substrates for α(2A)-AR inhibition of C1 neuron activity. Consistent with previous light microscopic studies, α(2A) AR-I was found in perikarya and large dendrites and the majority of these profiles also contained TH-labeling (~ 70% of 140). However, α(2A) AR-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 α(2A) AR-I profiles (n = 646) in the RVL were axons and axon terminals (~ 68%) which lacked TH immunoreactivity, α(2A) AR-labeled axons were small and unmyelinated and labeled terminals usually formed symmetric synapses on the shafts of catecholaminergic or unlabeled dendrites. Most of these α(2A) AR- labeled axons were found in close proximity to TH-labeled profiles and approximately one-fifth (17% of 408) of the α(2A) AR-labeled axons and axon terminals directly contacted TH-labeled profiles, mostly dendrites. These studies suggest that α(2A) ARs 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.
KW - C1 adrenergic neuron
KW - Catecholamine receptor
KW - Catecholaminergic axon
KW - Electron microscopy
KW - Reticulospinal neuron
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U2 - 10.1016/S0006-8993(98)00725-2
DO - 10.1016/S0006-8993(98)00725-2
M3 - Article
C2 - 10064804
AN - SCOPUS:0033528320
SN - 0006-8993
VL - 821
SP - 200
EP - 211
JO - Brain research
JF - Brain research
IS - 1
ER -