Quantitative densitometry of neurotransmitter receptors

Rainbow, Thomas C.; Bleisch, William V.; Biegon, Anat; McEwen, Bruce S.

doi:10.1016/0165-0270(82)90059-0

Cited by 164 publications

(41 citation statements)

References 13 publications

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“…The autoradiographic distribution of All receptors in rat brain was found to be unique and quite distinct from any other receptor distribution previously visualized (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). Further light-microscopic autoradiography is necessary to identify the cell type associated with these receptors.…”

Section: Discussionmentioning

confidence: 67%

Autoradiographic localization of angiotensin II receptors in rat brain.

Mendelsohn¹,

Quirion²,

Saavedra³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

442

209

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The 125I-labeled agonist analog [1-sarcosine]-angiotensin II ([Sar']AII) bound with high specificity and affinity (Ka = 2 x 109 M-1) to a single class of receptor sites in rat brain. This ligand was used to analyze the distribution of All receptors in rat brain by in vitro autoradiography followed by computerized densitometry and color coding. A very high density of All receptors was found in the subfornical organ, paraventricular and periventricular nuclei of the hypothalamus, nucleus of the tractus solitarius, and area postrema. A high concentration of receptors was found in the suprachiasmatic nucleus of the hypothalamus, lateral olfactory tracts, nuclei of the accessory and lateral olfactory tracts, triangular septal nucleus, subthalamic nucleus, locus coeruleus, and inferior olivary nuclei. Moderate receptor concentrations were found in the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial habenular nucleus, lateral septum, ventroposterior thalamic nucleus, median eminence, medial geniculate nucleus, superior colliculus, subiculum, preand parasubiculum, and spinal trigeminal tract. Low concentrations of sites were seen in caudate-putamen, nucleus accumbens, amygdala, and gray matter of the spinal cord. These studies have demonstrated that All receptors are distributed in a highly characteristic anatomical pattern in the brain. The high concentrations of All receptors at numerous physiologically relevant sites are consistent with the emerging evidence for multiple roles of All as a neuropeptide in the central nervous system.

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Section: Discussionmentioning

confidence: 67%

Autoradiographic localization of angiotensin II receptors in rat brain.

Mendelsohn¹,

Quirion²,

Saavedra³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

442

209

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“…The extent and duration of NMDAR activation in animal and human posttraumatic or postischemic brains have not been reported to date. Using modifications of the standard autoradiographic procedure for measuring NMDAR total density (29,30,36) that were designed to preserve the endogenous milieu [i.e., omission of tissue washing and exogenous glutamate and glycine (30)], we have been able to measure the density of endogenously activated (open channel) NMDAR with radioactive MK801. CHI did indeed increase the density of MK801 binding under these conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Scanned images were analyzed quantitatively (36,37) by using NIH IMAGE software. Anatomical regions underlying the autoradiographic images were identified on the consecutive brain sections stained with cresyl violet in reference to a mouse brain atlas (38).…”

Section: Methodsmentioning

confidence: 99%

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Biegon

Fry

Paden

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

219

164

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Traumatic brain injury is a leading cause of mortality and morbidity among young people. For the last couple of decades, it was believed that excess stimulation of brain receptors for the excitatory neurotransmitter glutamate was a major cause of delayed neuronal death after head injury, and several major clinical trials in severely head injured patients used blockers of the glutamate N-methyl-D-aspartate (NMDA) receptor. All of these trials failed to show efficacy. Using a mouse model of traumatic brain injury and quantitative autoradiography of the activity-dependent NMDA receptor antagonist MK801, we show that hyperactivation of glutamate NMDA receptors after injury is short-lived (<1 h) and is followed by a profound and long-lasting (>7 days) loss of function. Furthermore, stimulation of NMDA receptors by NMDA 24 and 48 h postinjury produced a significant attenuation of neurological deficits (blocked by coadministration of MK801) and restored cognitive performance 14 days postinjury. These results provide the underlying mechanism for the well known but heretofore unexplained short therapeutic window of glutamate antagonists after brain injury and support a pharmacological intervention with a relatively long (>24 h) time window easily attainable for treatment of human accidental head injury.H ead trauma is a leading cause of mortality and morbidity among young people in the western world (1). Traumatic and ischemic brain injury triggers a large, transient increase in excitatory amino acid transmitter efflux in the brain of experimental animals and human subjects (2-6). Glutamate activation of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which is a ligand-gated ion (calcium and sodium) channel, results in channel opening and ion influx into the cell. It has been suggested that this process mediates delayed excitotoxic neuronal death after brain ischemia and trauma (7,8), although the concept is not universally accepted (9, 10). Support for the involvement of NMDAR activation in neuronal death after brain injury has come from numerous studies showing that NMDAR antagonists reduce cell death and improve outcome in animal models of traumatic brain injury (TBI) and stroke. NMDAR antagonists appear to be most efficacious when given before or immediately after the insult and lose efficacy if administered Ͼ30-60 min postinjury (11)(12)(13)(14)(15).Microdialysis studies of extracellular glutamate in human TBI and stroke patients suggested that the increase in glutamate in humans is more sustained [6 h to several days (7, 8)] than in rodents, where it only lasts minutes (2-6). This result may have contributed to a decision to administer NMDAR antagonists in clinical trials of head injury for several days rather than once after severe nonpenetrating injury. All clinical trials of NMDAR antagonists to date failed to show efficacy. Furthermore, some of these trials had to be stopped prematurely because of increases in mortality and morbidity in the drug arm of the stroke trials (16-18), suggesting that prolonged bloc...

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“…Recent advances in autoradiographic methods introduced by Kuhar and coworkers [8] have made it possible to study receptor distribution in vitro in brain sections. A modification using tritium-sensitive sheet film has been introduced [9]. Based on this method preliminary reports have appeared showing that autoradiography of [3H]AVP binding sites is feasable [2,10,13].…”

mentioning

confidence: 99%

“…The brains were rapidly removed from the skull and frozen in dry ice. Tissue preparation and autoradiographic procedures were performed according to previously published methodology [9]. For autoradiographic localization 32 #m sections were preincubated for 20 min at room temperature in a 0.17 M Tris buffer, pH 7.6, containing 4 mM CaCI2.…”

mentioning

confidence: 99%

Arginine-vasopressin binding sites in rat brain: A quantitative autoradiographic study

Biegon

Terlou

Voorhuis

et al. 1984

Neuroscience Letters

120

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Specific binding sites for arginine-vasopressin (AVP) were detected in rat brain after incubation of tissue sections with [3H]AVP. AVP and two selective AVP antagonists are capable of displacing [3H]AVP with an ICso in the 10-s-10 -7 molar range, while oxytocin and ACTH4-l0 were much less effective. The neuroanatomical distribution of [3H]AVP-labeled sites was studied with autoradiography utilizing tritium-sensitive LKB film and computerized densitometry for quantitative analyses of the film images. The highest density of [3H]AVP binding sites was observed in hippocampal regions, the lateral septum, olfactory and amygdaloid nuclei, and the nucleus tractus solitarii (NTS) of the brainstem.Arginine-vasopressin (AVP) influences memory processes [4,6]. This action of AVP takes place in certain discrete limbic-midbrain regions [7]. AVP also acts on biochemical and electrophysiological processes in these areas. It was found that the peptide affects indices for catecholamine turnover in the hippocampal dentate gyrus, dorso-lateral septum and nucleus tractus solitarii (NTS) [7,12], and alters the firing pattern of neurons in the lateral septum [5]. Immunocytochemical studies have demonstrated that these limbic-midbrain regions are innervated by AVPcontaining neurons [3]. Recent advances in autoradiographic methods introduced by Kuhar and coworkers [8] have made it possible to study receptor distribution in vitro in brain sections. A modification using tritium-sensitive sheet film has been introduced [9]. Based on this method preliminary reports have appeared showing that autoradiography of [3H]AVP binding sites is feasable [2,10,13]. In the present *On leave of absence from the

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Quantitative densitometry of neurotransmitter receptors

Cited by 164 publications

References 13 publications

Autoradiographic localization of angiotensin II receptors in rat brain.

Autoradiographic localization of angiotensin II receptors in rat brain.

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

Arginine-vasopressin binding sites in rat brain: A quantitative autoradiographic study

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