Search PubMed⌕ Search

Biomedical subjects

M J Brownstein

Publications and source records attributed to M J Brownstein.

At least 109 records · Page 6Linked to original sources
PubMed1982

Origin of the cholecystokinin-containing fibers in the rat caudatoputamen.

Large Amounts of cholecystokinin-octapeptide (CCK) are present in the rat caudatoputamen. The peptide occurs in axons and nerve endings but not in perikarya. The origin of CCK in the caudatoputamen was investigated with the use of immunocytochemistry and a radioimmunoassay specific for CCK. Although a small amount of CCK (approximately 30 percent) originates in the amygdaloid complex, the bulk of the peptide (approximately 70 percent) occurs in processes of neurons located ventral to the caudatoputamen, that is, the claustrum or the piriform cortex. The claustrum and piriform cortex receive inputs from various cortical areas and the olfactory system, respectively, and may process information and relay it to the caudatoputamen. Thus CCK may by the transmitter in the final common pathway linking various cortical areas and the olfactory system to the caudatoputamen.

Amygdala↗
PubMed1982

High-affinity binding of [3H]desipramine to rat brain: a presynaptic marker for noradrenergic uptake sites.

High-affinity binding sites (apparent KD = 1.5 nM) for [3H]desipramine have been demonstrated and characterized in membranes prepared from rat brain. The binding of [3H]desipramine was found to be saturable, reversible, heat-sensitive, sodium-dependent, and regionally distributed among various regions of the brain. High concentrations of [3H]desipramine binding sites were found in the septum, cerebral cortex, and hypothalamus, whereas lower concentrations were found in the medulla, cerebellum, and corpus striatum. A very good correlation (r = 0.81, P less than 0.001) was observed between the potencies of a series of drugs in inhibiting high-affinity [3H]desipramine binding and their capacity to block norepinephrine uptake into synaptosomes. In 6-hydroxydopamine-lesioned rats there was a marked decrease in [3H]norepinephrine uptake and [3H]desipramine binding with no significant alterations in either [3H]serotonin uptake or [3H]imipramine binding. These results suggest that the high-affinity binding of [3H]desipramine to rat brain membranes is pharmacologically and biochemically distinct from the high-affinity binding of [3H]imipramine, and that there is a close relationship between the high-affinity binding site for [3H]desipramine and the uptake site for norepinephrine.

Animals↗
PubMed1982

The course of thyrotropin-releasing hormone fibers to the median eminence in rats.

The topographical distribution of fibers containing TRH that run to the median eminence has been investigated by RIA of TRH after hypothalamic surgical transections in rats. Anterolateral or lateral cuts bilaterally transecting fibers at the caudal edge of the optic chiasm (lateral retrochiasmatic area) diminish TRH levels in the median eminence by 95% and 73%, respectively. Paramedian cuts are ineffective. These results suggest that TRH fibers reach the medial basal hypothalamus from an anterolateral direction just as several other classes of peptide containing fibers do.

Animals↗
PubMed1981

Injection of alpha-bungarotoxin near the suprachiasmatic nucleus blocks the effects of light on nocturnal pineal enzyme activity.

Environmental lighting can prevent or quickly reverse the nocturnal elevation of serotonin N-acetyltransferase activity in the rat pineal gland. Intraventricular injections of carbachol, acting via a 'nicotonic' cholinergic receptor, mimic the acute effect of light. Injections of alpha-bungarotoxin near the suprachiasmatic nucleus of the hypothalamus prevent the effects of light. These results suggest that acetylcholine is involved in the effects of light on the rat pineal's circadian rhythm.

Acetyltransferases↗
PubMed1981

The distribution of cholecystokinin immunoreactivity in the central nervous system of the rat as determined by radioimmunoassay.

The regional distribution of cholecystokinin (CCK) in the rat brain was determined utilizing a radioimmunoassay which detects both gastrin and CCK. CCK concentration is highest in the caudate nucleus (10-14 ng CCK 8 equivalents/mg protein), followed by the cerebral cortex. Within the cerebral cortex, CCK is highest in the cingulate, pyriform, and entorhinal areas. There are substantial CCK concentrations in all other brain regions except pons, medulla and cerebellum. CCK is widely distributed in the hypothalamus, where it is highest in the median eminence and ventromedial nucleus. Considerable CCK-like immunoreactivity is also present in the posterior lobe of the pituitary gland, but is not detectable in anterior and intermediate lobes. Though the antisera used in this study cross-react with gastrin the dominant CCK-like material found in rat brain co-elutes with sulfated CCK 8 and separates from gastrin on Sephadex G-25 and HPLC chromatography.

Animals↗
PubMed1981

Time course of appearance and release of [35S]cysteine labelled neurophysins and peptides in the neurohypophysis.

[35S]cysteine injected adjacent to the supraoptic nuclei (SON) of rats is rapidly incorporated into two macromolecular (both about 20,000 Daltons) common precursors of arginine vasopressin (AVP) and its associated neurophysin, and oxytocin (OT) and its neurophysin. Conversion of the larger precursor proteins to the smaller peptides appears to occur intragranularly during axonal transport to the neurohypophysis. The labelled products of this conversion (neurophysin, AVP, and OT) are released, in a Ca2+-dependent manner, from the posterior pituitary in response to depolarization by veratridine. Both the rates of biosynthesis and of processing of the precursors are greatly increased by increased functional activity (i.e. secretion) of the hypothalamo--neurohypophysial system.

Animals↗
PubMed1981

Multiple-rate components of axonally transported proteins in the hypothalamo-neurohypophysial system of the rat.

The transport of labeled proteins from the hypothalamus to the neurohypophysis following 35S-methionine injection into the rat supraoptic nucleus was studied using a unique approach adapted for the study of short-axon systems. Multiple-rate components to those found in other neuronal systems were demonstrated. Neurosecretory vesicle-containing proteins (e.g., neurophysins) were transported at fast rates (greater than 120 mm/day), whereas the cytoskeletal protein, actin, moved principally in the slow component of transport. Two-dimensional gel electrophoresis was used to analyze the diverse patterns of labeled proteins found in the various rate components of axonal transport in this system.

Actins↗
PubMed1981

Cholecystokinin in the central nervous system.

We have used high performance liquid chromatography and radioimmunoassay to characterize the CCK-like molecules in the central nervous system. The major form of CCK is the sulfated octapeptide. This molecule is distributed unevenly among various brain regions; the highest levels are found in the cortex and striatum. We have focused our attention on three areas in particular, the posterior pituitary, the caudate nucleus, and the hippocampus. The first of these receives its CCK-containing fibers from the hypothalamic magnocellular nuclei, the second appears to be innervated by the claustrum (or piriform cortex). The CCK in the hippocampus, on the other hand, is in intrinsic neurons. These structures and others in the brain have CCK binding sites.

Animals↗
PubMed1981

Decrease of glutamate decarboxylase (GAD)-immunoreactive nerve terminals in the substantia nigra after kainic acid lesion of the striatum.

Antiserum sheep 3 against rat brain glutamate decarboxylase (GAD) was employed for the immunohistochemical localization of GAD-immunoreactive nerve terminals in the substantia nigra (SN). To test whether the antiserum specifically localized GAD-containing axon terminals, the effect of kainic acid-induced striatal lesions on the reactive nerve endings in the SN was investigated. Seven days after the injection of 1 microgram kainic acid into the striatum, a 65% decrease in GAD-enzyme activity occurred in the ipsilateral SN. On immunohistochemical examination there was correspondingly a marked reduction of GAD-positive terminals. The parallel decrease in biochemical and immunohistochemical GAD activity indicates that antiserum sheep 3 can be used as a specific immunohistochemical probed for GAD-containing elements.

Animals↗
PubMed1981

Extrahypothalamic distributions and functions of hypothalamic peptide hormones.

The isolation and chemical identification of the hypothalamic hormones somatostatin, luteinizing hormone-releasing factor (LRF), and thyrotropin-releasing factor (TRF) within the last decade have allowed the chemical synthesis of these compounds and the development of radioimmunoassay and immunohistochemical methods for them. As a result, these "hypothalamic" hormones have been detected in many extrahypothalamic locations, including brain and gastroenteropancreatic tissues. The hypothalamoneurohypophysial hormones vasopressin and oxytocin have also been localized in extrahypothalamic neuronal pathways. It has become clear that these neuropeptides subserve multiple endocrine and neurotransmitter functions outside the hypothalamus. The information now available about the extrahypothalamic distributions and possible physiological roles of somatostatin, TRF, LRF, vasopressin, and oxytocin is reviewed.

Animals↗
PubMed1980

Cholecystokinin octapeptide in the rat hypothalamo-neurohypophysial system.

Gastrin-cholecystokinin (CCK)-like immunoreactivity has been visualized by immunohistochemistry in the vasopressin-oxytocin neurosecretory system comprising the posterior lobe of the pituitary, the supraoptic and paraventricular nuclei of the hypothalamus. This CCK-like substance has not been chemically identified in the rat, but has been reported to be gastrin 17 in the swine pituitary. We report here that this CCK-like immunoreactive substance co-chromatographs with CCK8 sulphate on Sephadex G-50 and two HPLC chromatographic systems. No gastrin 17 was detected in rat pituitary or brain. We further report that about 60% of the CCK in posterior lobe originates in cell bodies in the paraventricular nucleus of the hypothalamus. The CCK content of posterior pituitary is dramatically decreased by physiological perturbations which stimulate vasopressin or oxytocin release. We propose that CCK may either be co-secreted with vasopressin and oxytocin to act on peripheral targets or may be involved in the regulation of vasopressin or oxytocin neurosecretion.

Animals↗
PubMed1980

Peptidergic pathways in the central nervous system.

Before detailed studies of the physiology and pharmacology of central peptidergic neurons can be undertaken, the location of these neurons must be determined and the mechanism(s) by which they synthesize their peptide products must be explored. In the previous paper, Dr Hökfelt described his elegant immunohistochemical studies, which are designed to answer the questions: Where are peptidergic perikarya?; Where do these perikarya send their processes?; Do these processes branch extensively and innervate several structures?; and Do peptidergic cells contain more than one active product? By studying the effects of lesions on peptide levels in microdissected tissue samples, immunocytochemical data can be confirmed and extended. The microanalytical approach also allows one to determine the nature of the immunologically active substances in a tissue extract, and in vivo or in vitro pulse--chase studies provide the ultimate validation of immunohistological localization of peptidergic perikarya and new information about the biosynthesis of peptides and regulation of this biosynthetic process. Our recent studies of central proopiocortin- and neurophysin/vasopressin-producing neurons will illustrate the above points.

Adrenocorticotropic Hormone↗
PubMed1980

Deafferentation studies on the glutamic acid decarboxylase content of the supraoptic nucleus of the rat.

The localization of the GABAergic neurons which send efferent fibers to the supraoptic nucleus was investigated. For this purpose the activity of glutamic acid decarboxylase, a specific marker for GABAergic neurons, was determined in the supraoptic nucleus after a variety of lesions. The severance of fibers from the mesencephalon and the mediobasal hypothalamus, as well as from the hippocampus, had no effect. However, lesions rostral to the nucleus reduced its activity in glutamic acid decarboxylase by about 40%, as did the infusion of kainic acid into the nucleus accumbens. Thus, the neurons in the supraoptic nucleus seem to receive a large part of their GABAergic afferents from the n. accumbens. In addition to that, GABAergic neurons intrinsic or adjacent to the supraoptic nucleus seem to contribute to the regulation of the release of vasopressin and/or oxytocin.

Afferent Pathways↗
PubMed1980

Effect of surgical deafferentation of the supraoptic nucleus on its choline acetyltransferase content.

The concentration of choline acetyltransferase, a specific marker for cholinergic neurons, was determined in the supraoptic nucleus after a variety of lesions. Surgical lesions immediately rostral as well as medial and lateral to the nucleus did not affect the concentration of the enzyme. Only lesions which separated the nucleus from the posterior part of the lateral hypothalamus slightly decreased its concentration in choline acetyltransferase. It is concluded that the bulk of the cholinergic neurons is in the supraoptic nucleus or its immediate vicinity.

Afferent Pathways↗