Expression of adrenergic receptors in individual astrocytes and motor neurons isolated from the adult rat brain

Abstract

Attempts to show the distribution of adrenergic receptors (ARs) in autoradiographs of a brainstem motor nucleus following elimination of motor neurons yielded the unexpected result of an increase in beta-AR density. This increase was related to the gliosis accompanying the motor neuron degeneration. To determine the cells on which the AR subtypes were located, we dissociated cells from various regions of the adult rat brain and subsequently identified astrocytes by glial fibrillary acidic protein (GFAP) immunofluorescence. Slides containing the astrocytes were prepared for autoradiography using the nonselective beta ligand 125I-iodocyanopindolol (125ICYP) or the alpha 1 ligand 125IBE 2254 (125I-HEAT). The addition of the selective beta 1 blocker betaxolol or the beta 2 blocker ICI 118.551 to the incubation medium to displace 125ICYP binding was used to determine the binding of beta-AR subtypes. The great majority (greater than 88%) of isolated astrocytes sampled from the trigeminal motor nucleus, cerebral cortex, striatum, and cerebellum showed beta-AR binding. Astrocytes from the first three regions had similar average densities of beta-ARs, whereas the density in cerebellar astrocytes was 2- to 3-fold greater. The beta 2-AR subtype was proportionally greater than the beta 1 subtype in each region. Reactive astrocytes isolated from the trigeminal motor nucleus after degeneration of motor neurons showed a beta-AR density nearly 2-fold greater than resting astrocytes from the same region, with the beta 1 subtype showing the greater proportional increase. There was no beta-AR binding on trigeminal motor neurons. Astrocytes also showed a significant level of alpha 1-AR binding. No differences in alpha 1-AR binding were found in normal astrocytes isolated from the different regions, nor was there an increase in reactive astrocytes. In contrast, trigeminal motor neurons had an alpha 1-AR density nearly 10 times greater than astrocytes. In terms of the NE modulation of synaptic responses in motor neurons, the distribution of ARs would permit NE to act indirectly through alpha 1 and beta receptors on astrocytes and directly through alpha 1 receptors on motor neurons.

Evidence for altered central noradrenergic function in experimental acute liver failure in the rat

“…Astrocytes express ␣ and ␤ adrenergic receptor subtypes both in culture 36 and in situ. 37 ␤ receptors in mammalian brain are localized not only on neuronal membranes, but also on astrocytes. 36 Astrocytes have the ability to rapidly change their shape in response to changes in their chemical and cellular environment.…”

Astrocytic β 2 -adrenergic receptors mediate hippocampal long-term memory consolidation

“…17). However, in addition to being expressed in pre-and postsynaptic compartments of neurons, βARs are also found in other cell types, particularly in astrocytes (18)(19)(20)(21). More specifically, it has been suggested that β 2 ARs in the nervous system are expressed predominantly in glia (18,(21)(22)(23), whereas β 1 ARs are found primarily in neurons, at synaptic junctions (18,22,23).…”

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

“…A high density of β-adrenergic receptors has also been demonstrated in the trigeminal motor nucleus, where β 2 -adrenergic receptors dominate [170]. After neuronal damage there is an increase in β-adrenergic receptor expression on astrocytes, with the greater proportional increase occurring in β 1 -adrenergic receptors.…”

“…Later studies, using an antibody specifically to the C-terminal tail of the β 2 -adrenergic receptor (but recognizing both β 1 -and β 2 -adrenergic receptors) showed in visual cortex a predominant localization of the receptor on small astrocytic processes contacting catecholaminergic axon terminals [162][163]. Pronounced expression of β-adrenergic receptors has also been demonstrated by aid of the receptor ligand [ 125 I]iodocyanopindolol in both cerebral cortex, striatum and cerebellum, with the highest receptor density on cerebellar astrocytes [164]. In the kitten visual cortex close to one half of all β-adrenergic receptors were found on astrocytes [165].…”

“…Mouse brain astrocytes in primary cultures express α 1 -adrenergic receptors [181][182], although the binding density is less than that found for β-adrenergic receptors, and α 1 -adrenergic receptors are not present on all individual astrocytes [183]. α 1 -Adrenergic receptors have also been described on freshly isolated astrocytes [157,164] from different brain areas as well as from the trigeminal motor nucleus, where they decrease following neuronal injury [170].…”