Biomedical subjects

T C Rainbow

Publications and source records attributed to T C Rainbow.

At least 19 recordsLinked to original sources

PubMed1986

The ontogeny of the laminar distribution of beta-adrenergic receptors in the visual cortex of cats, normally reared and dark-reared.

Patterns of distribution of beta 1 and beta 2 adrenergic receptors were examined autoradiographically in slide-mounted sections from the visual cortical areas of 22 developing cat brains, using [125I]iodopindolol as the ligand in combination with displacers specific for beta 1 and beta 2 subtypes of adrenergic receptors. Within visual cortical areas 17 and 18 of adult brains, the density of beta 1 and beta 2 adrenergic receptors was highest in laminae I-III, lowest in lamina IV, and intermediate in laminae V-VI. For beta 1 adrenergic receptors, this laminar distribution was also seen in visual area 19 as well as in the non-visual area 7 that is lateral to area 19. By contrast, the distribution of beta 2 adrenergic receptors varied across cortical areas, such that its density was more homogeneous across the laminae in area 19, and decreased in all laminae in area 7. This pattern of distribution in adult brains was already formed at the beginning of the critical period and was not disturbed by dark-rearing.

Animals↗

PubMed1986

Identification of sodium-dependent, high-affinity choline uptake sites in rat brain with [3H]hemicholinium-3.

[3H]Hemicholinium-3 (HC-3) was used to label sodium-dependent, high-affinity choline uptake sites in regions of rat brain. Autoradiography revealed a high density of [3H]HC-3 binding sites in brain regions with a high density of cholinergic terminals, such as the interpeduncular nucleus, caudate-putamen, and olfactory tubercle. This distribution of [3H]HC-3 binding sites was in close agreement with the amounts of choline acetyltransferase in specific nuclei and subregions of rat brain. Destruction of presynaptic cholinergic projections in the cerebral cortex and the basal ganglia by injection of excitotoxins reduced [3H]HC-3 binding by 40-50%. These data indicate that sodium-dependent [3H]HC-3 binding sites are related to the choline transport system present in cholinergic neurons.

Animals↗

PubMed1986

Aldosterone effects on salt appetite in adrenalectomized rats.

In order to establish the in vivo specificity of the mineralocorticoid recognition system of the rat brain, we investigated the potencies of aldosterone (ALDO) and corticosterone (CORT) in suppressing salt intake in adrenalectomized (ADX) rats. Increasing doses of ALDO (25, 50 and 100 ng/h), administered by Alzet minipump, suppress salt intake in a two-bottle preference test. CORT in doses up to 50 micrograms/h failed to mimic this effect of ALDO or to block it. Using the 50 micrograms/h dose of CORT, we demonstrated that the forebrain uptake of 3H-ALDO in vivo is suppressed by 60-75% when measured by isolation of cell nuclei or by quantitative autoradiography. The suppression is especially marked in the hippocampal formation, amygdala and septum, sites which also accumulate high levels of 3H-CORT. The uptake of 3H-ALDO by ADX rat forebrain can be suppressed approximately 95% by infusion of a specific antimineralocorticoid, RU 28318, at a dose of 50 micrograms/h. This dose also blocks ALDO action on salt intake. Lower doses of RU 28318 fail to block ALDO action or brain 3H-ALDO uptake. We conclude that: (1) ALDO is at least 500-fold more potent in vivo than CORT as a mineralocorticoid. (2) High uptake of 3H-ALDO in vivo by hippocampal formation, amygdala and septum in ADX rats is due in large part to binding to sites preferentially suppressed by CORT. The 3H-ALDO uptake (ca. 30%) after suppression by stress levels of CORT shows a regional distribution in which uptake is slightly higher in circumventricular structures than in hippocampal formation, septum or amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1986

Autoradiographic localization of thyrotropin releasing hormone receptors in human brain.

We used quantitative autoradiography to localize thyrotropin releasing hormone (TRH) receptors in human brain. Highest concentrations of TRH receptors were localized within the cortical, basal, and lateral nuclei of the amygdala and the molecular layer of the hippocampus. Low levels were found in the cortex, diencephalon, and basal ganglia. The radioligand bound with similar affinity and pharmacology to pituitary gland as to brain. These data suggest that authentic TRH receptors in the hippocampus and amygdala may mediate the putative effects of TRH on the human brain.

Aged↗

PubMed1986

Localization and quantification of beta-adrenergic receptors in human brain.

Little information is currently available on the localization of noradrenergic systems in the human CNS. We used quantitative autoradiography with [125I] iodopindolol to examine beta-adrenergic receptors in postmortem human brain. The concentration of beta-receptors was highest in all subfields of the hippocampus, followed by cerebellum, and then thalamic nuclei, basal ganglia, midbrain, and cerebral cortex. Low levels were found in white matter and hypothalamus. This distribution differed from the distribution of beta-receptors reported in membrane homogenates of human brain and also from the distribution of beta-receptors in rat brain determined by autoradiography. The similarities and differences between the distribution of beta-receptors in the human and rat brains may have implications regarding the role of norepinephrine in the CNS of these two species.

Aged↗

PubMed1985

Further studies of brain aldosterone binding sites employing new mineralocorticoid and glucocorticoid receptor markers in vitro.

We have used synthetic markers of the glucocorticoid (GC) receptor (RU 28362) and of the mineralocorticoid (MC) receptors (RU 26752 and RU 28318) to characterize the specificity of the sites binding aldosterone (ALDO), dexamethasone (DEX) and corticosterone (CORT) in cytosol of hippocampus. The results obtained suggest that ALDO was bound mostly to a MC receptor, as the relative binding affinity (RBA) of the GC receptor marker (and that of the previously studied RU 26988) was negligible for this site, in contrast to the high RBA displayed by RU 26752. DEX was bound for a large part to a GC receptor, as RU 28362 competed for this site, although the MC receptor marker still showed some affinity. An intermediate effect of both marker types was obtained with CORT. RU 28318 was a weak competitor for either the GC or the MC binding site. Thus, RU 28362 and RU 26752 allowed the discrimination of two to three receptors in the hippocampus, similarly to those described in the kidney. Finally, we have demonstrated the usefulness of these synthetic markers in identifying MC binding sites in several brain regions and also in the hippocampus during ontogenetic development.

Adrenalectomy↗

PubMed1985

Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study.

The effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on neurotransmitter receptors was studied in dorsal hippocampus of rat using quantitative autoradiography. ADX for one week causes an increase in [3H]5-HT binding to 5-HT1 receptors which is significant in the CA1 cell field. CORT treatment of ADX rats for 3-5 days results in localized reductions of [3H]5-HT binding including a partial reversal of the increase observed after ADX in CA1. CORT treatment of ADX animals also decreases binding of [3H]QNB to muscarinic receptors in the dorsal hippocampus, with a significant effect in an area designated as subiculum. No influence of CORT was detected on [3H]prazosin binding to alpha 1 adrenergic receptors in dorsal hippocampus. Possible mechanisms for hormone effects on neurotransmitter receptor levels are discussed.

Adrenalectomy↗

PubMed1985

Localization in rat brain of binding sites for parkinsonian toxin MPTP: similarities with [3H]pargyline binding to monoamine oxidase.

A high-affinity binding site exists in rat brain for the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The pharmacological specificity of this binding site suggests that it may correspond to monoamine oxidase (MAO). We have used quantitative autoradiography to map in detail the anatomical distribution of the [3H]MPTP binding site in rat brain and compared it with the anatomical distribution of MAO as determined by in vitro autoradiography with [3H]pargyline. Under the conditions of the assay, [3H]pargyline labeled the type B form of MAO. There were strong similarities in the anatomical distribution of [3H]MPTP and [3H]pargyline, with high levels of both binding sites occurring in the arcuate nucleus, the locus coeruleus, the dorsal raphe nucleus and all circumventricular organs. Low levels of both binding sites were found in the substantia nigra and the caudate-putamen. These results provide additional evidence that the high-affinity binding site for MPTP is MAO. The parkinsonian actions of MPTP might result from metabolites produced by MAO.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1985

Blockade of peripheral beta-adrenergic receptors fails to suppress the cerebral spread of an engram in mice.

Using bitemporal injections of puromycin, we have reported observations interpreted to indicate that a systemic injection of (-)-propranolol (50 micrograms/kg) drastically suppressed the spread of an engram in mice from the hippocampalentorhinal area to widespread cerebral areas. The present experiments were made with a non-selective, irreversible beta-adrenergic receptor antagonist that fails to cross the blood-brain barrier in order to test the possibility that the propranolol-induced blockade of peripheral beta-receptors might contribute to its effect on engram spread. Prolonged blockade of peripheral receptors by the irreversible antagonist had no effect on engram spread, suggesting that propranolol's effect was centrally mediated.

Animals↗

PubMed1985

Microcomputer-assisted densitometer for quantitative receptor autoradiography.

We describe here a simple, inexpensive microcomputer-assisted densitometer for use with quantitative receptor autoradiography. The resolution of this system is approximately 100 micron. With this system, and an accompanying program DENSIT, it is relatively easy to convert density values of autoradiograms into molar quantities of bound ligand. The general design of the system and the logic of the DENSIT program are applicable to a variety of hardware systems.

Animals↗

PubMed1985

Blockade of beta 1- but not of beta 2-adrenergic receptors replicates propranolol's suppression of the cerebral spread of an engram in mice.

Bitemporal injections of puromycin that primarily affect the hippocampal-entorhinal area induce amnesia of aversive maze-learning in mice for 3 days after training but are ineffective 6 or more days after training. At these later times, additional puromycin sites covering widespread forebrain areas are necessary to induce amnesia, a result that we attribute to the cerebral spread of the engram during the 6-day period. We have reported that blockade of about 60% of cerebral beta-adrenergic receptors by a single, subcutaneous injection of (-)-propranolol, a nonselective beta-receptor antagonist, inhibited engram spread for 60-90 days, at which time engram spread spontaneously occurred. In the present experiments using single doses of antagonists that appeared to block 60% of beta 2- or beta 1-adrenergic receptors, it was found that the selective beta 2 antagonist ICI 118,551 was without effect on engram spread, whereas the selective beta 1 antagonist betaxolol inhibited the spread for at least 3 months. Propranolol's effect consequently appears to be accounted for by its blockade of beta 1 receptors.

Adrenergic beta-Antagonists↗

PubMed1985

Similar distribution of monoamine oxidase (MAO) and parkinsonian toxin (MPTP) binding sites in human brain.

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and other species. We found [3H] MPTP binding sites that were saturable, specific, and of high affinity. In autoradiographic studies, the highest binding densities of [3H] MPTP occurred in the hypothalamus, interpeduncular nucleus, and ependymal lining of the ventricles. High to moderate binding was seen in the dentate gyrus, caudate, putamen, substantia nigra, and cingulate cortex. The distribution of [3H] MPTP binding correlated with the distribution of [3H] pargyline binding to MAO. Human substantia nigra contains more MPTP binding sites than rat substantia nigra, and this may explain the sensitivity of humans to the neurotoxic effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1985

Autoradiographic localization of thyrotropin-releasing hormone receptors in amyotrophic lateral sclerosis spinal cord.

We used quantitative autoradiography to determine the density of thyrotropin-releasing hormone (TRH) receptors in discrete regions of spinal cord from four patients with amyotrophic lateral sclerosis (ALS). The density and distribution of [3H]-3-methyl-histidine-TRH binding to TRH receptors differed from reported values in normal individuals, with fewer TRH receptors in lamina II and lamina IX. The diminished concentration of TRH receptors in lamina IX may reflect the loss of motor neurons in ALS.

Amyotrophic Lateral Sclerosis↗

PubMed1985

Autoradiographic localization of thyrotropin-releasing hormone (TRH) receptors in human spinal cord.

Thyrotropin-releasing hormone (TRH) exerts many effects upon spinal cord function in animals, and may also play a role in human spinal cord function. We have used the technique of quantitative autoradiography to anatomically localize specific receptors for TRH within human spinal cord. Highest concentrations of TRH receptors were localized within lamina II, the substantia gelatinosa. A moderate density of TRH receptors was found in lamina IX, the motor neurons of the anterior horn. Low levels of TRH receptors were noted throughout the remainder of the gray matter of the human spinal cord, and no TRH receptors were localized within white matter. This anatomic distribution of TRH receptors within the human spinal cord is consistent with the localization of endogenous TRH and the effects of exogenously applied TRH in animal studies. These results suggest that any effects of TRH on human spinal cord function may be mediated by TRH receptors.

Aged↗

PubMed1985

Autoradiographic localization of thyrotropin-releasing hormone receptors in the rat central nervous system.

We employed quantitative autoradiography to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat CNS. The binding of [3H]3-methyl-histidine-TRH [( 3H]MeTRH) to TRH receptors in frozen rat brain sections was saturable, of a high affinity (Kd = 5 nM), and specific for TRH analogs. Autoradiograms of [3H]MeTRH binding showed highest concentrations of TRH receptors in the rhinencephalon, including accessory olfactory bulb, nuclei of the amygdala, and the ventral dentate gyrus and subiculum of the hippocampus. Moderate TRH receptor concentrations were found within the thalamus and hypothalamus, in most regions of the rhombencephalon, such as the cranial nerve nuclei, and in the substantia gelatinosa of the spinal cord. Neocortex and basal ganglia contained low densities of TRH receptors. This distribution correlates well with the sensitivity of brain regions to the known effects of TRH, and suggests that TRH receptors may mediate the actions of TRH in the rat CNS.

Amygdala↗

PubMed1984

Quantitative autoradiography of [3H]ouabain binding sites in rat brain.

In vitro quantitative autoradiography was used to localize in rat brain binding sites for [3H]ouabain, an inhibitor of the Na+,K+-ATP-ase. High levels of [3H]ouabain binding sites were found in the superior and inferior colliculi, the mammillary nucleus, the interpeduncular nucleus, and in various divisions of the olfactory, auditory and somatomotor systems. The heterogeneous distribution of [3H]ouabain binding closely parallels the regional brain glucose consumption as determined by the [14C]deoxyglucose method. Lesion studies of the rat hippocampus using the excitotoxin, ibotenic acid, showed both a marked decrease of neuronal cell types on the injected side and a corresponding decrease in [3H]ouabain binding, indicating that some of the [3H]ouabain binding sites are localized to neurons. The close correlation between [3H]-ouabain binding and regional glucose utilization provides further evidence for a linkage between glucose utilization and the neuronal Na+,K+-ATPase.

Animals↗

PubMed1984

Age-related changes in cytoplasmic estradiol receptor concentrations in microdissected brain nuclei: correlations with changes in steroid-induced sexual behavior.

The purpose of this study was to; determine at what age changes in cytoplasmic estradiol receptors are evident in specific microdissected brain areas of the female rat; assess whether alterations parallel previous changes observed when large brain areas were used for determination of receptor concentrations; and assess whether changes in cytoplasmic estradiol receptors are correlated with changes in steroid-mediated physiological functions. To assess the effects of age on cytoplasmic estradiol receptor concentrations, we used virgin female Sprague-Dawley rats at 3-4 months, 7-8 months and 10-11 months of age. They were ovariectomized 7-14 days prior to use to allow maximal translocation of receptors to the cytoplasm. The animals were anesthetized and perfused with a 10% (v/v) solution of dimethylsulfoxide to protect the receptor proteins from the effects of freezing. Brains were removed and frozen. This procedure of freezing the brains caused a minimal (15-18%) loss in the number of receptors and no change in the dissociation constant. Consecutive 300 micron sections were sliced and the following nuclei and brain areas were microdissected: bed nucleus of the stria terminalis, suprachiasmatic-preoptic area, medial preoptic nucleus, periventricular preoptic nucleus, periventricular anterior hypothalamic area, paraventricular nucleus, dorsomedial nucleus, ventromedial nucleus, arcuate-median eminence, medial amygdala, and cortical amygdala. The pituitary gland was also removed and analyzed. The cytoplasmic fraction from a tissue pool from 3 animals was prepared and aliquots were incubated with [3H]estradiol at a final concentration of 1.5 nM in the presence or absence of 100-fold excess moxestrol. Receptor-bound [3H]estradiol was separated from free hormone by gel filtration.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1984

Quantitative autoradiography of nicotinic [3H]acetylcholine binding sites in rat brain.

Quantitative autoradiography was used to localize nicotinic [3H]acetylcholine (ACh) binding sites in rat brain. High concentrations of nicotinic [3H]ACh binding sites were observed in the anterior and medial nuclei of the thalamus, the medial habenula and the superficial layer of the superior colliculus. Moderate levels of binding sites were observed in a variety of brain regions such as the frontoparietal cortex and the hippocampus. Low levels of nicotinic ACh sites occurred throughout the hypothalamus and the primary olfactory cortex.

Acetylcholine↗