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R D Ciaranello

Publications and source records attributed to R D Ciaranello.

At least 73 records · Page 4Linked to original sources
PubMed1983

Genetic control of dopamine and serotonin receptors in brain regions of inbred mice.

In this report the genetic determinants of dopamine and serotonin receptors are investigated. We have used two types of radioreceptor binding assays to identify and quantify these neurotransmitter receptors in various brain regions of inbred mice. In the first method dopamine and serotonin sites are quantified using [3H]spiperone in the presence of appropriate blanking agents. These results are compared with those obtained by the use of [3H]domperidone and [3H]mianserin to label D2 and S2 sites, respectively. Both methods yield nearly identical results. Strain differences in D2 sites are found in the striatum, olfactory tubercle and pituitary. The density of dopaminergic sites is uncorrelated in the 3 brain regions in all mouse strains studied, suggesting that genetic determination of receptor density is independently regulated in each region. Similar observations have been made for S2 receptors in the striatum, hypothalamus, olfactory tubercle and frontal cortex. Analysis of D3 and D2 binding sites in recombinant inbred lines suggests that each site may be determined monogenically.

Animals↗
PubMed1983

Platelet alpha 2-adrenergic receptor sensitivity in major depressive disorder.

We have investigated the functioning of alpha 2-adrenergic receptors in patients with major depressive disorder by measuring the specific binding of 3H-yohimbine, an alpha 2-adrenergic receptor antagonist, to platelet membranes. Bmax and Kd values for platelet 3H-yohimbine binding were normal in unmedicated patients with major depressive disorder, and did not correlate with scores on the Hamilton rating scale for depression. Platelet alpha 2-adrenergic antagonist sites were also unchanged in number or affinity in depressed patients after long-term treatment with a variety of antidepressant medications.

Antidepressive Agents↗
PubMed1983

Solubilization and characterization of high-affinity [3H]serotonin binding sites from bovine cortical membranes.

High-affinity [3H]serotonin binding activity has been solubilized from bovine cerebral cortical membranes by using Triton X-100, Tween-80, and octyl-beta-D-glucopyranoside. This mixture of detergents solubilizes the high-affinity [3H]serotonin binding activity present in crude membrane preparations with retention of 75-90% specific binding. The detergent mixture was chosen because it can easily be removed from the solubilized fraction by dialysis and polystyrene bead adsorption, thus permitting further purification and isolation of the binding sites. Saturation analysis reveals multiple components of high-affinity [3H]serotonin binding. In crude bovine cortical membranes, at least two binding components are present. A higher-affinity binding component, as defined from curvilinear Scatchard plots, has a Kd for [3H]serotonin of 1-3 nM, whereas a lower-affinity component has a Kd of 10-20 nM. In the solubilized preparation, only a single class of binding sites is apparent, with a Kd of 50-100 nM. Removal of detergents by dialysis and polystyrene bead adsorption results in restoration of the curvilinear Scatchard plot with apparent Kds similar to those observed in crude membrane preparations and with increased Bmax values for each component. [3H]Serotonin binding activity in the solubilized preparation is stable to Sephacryl S-300 column chromatography and to glycerol gradient sedimentation. Saturation analysis of the peak binding fractions from both these procedures once again yields curvilinear Scatchard plots, indicating that the multiple high-affinity binding components are preserved and migrate together. The molecular weight, Stokes radius, and frictional coefficient of the binding site(s) have been calculated. After detergent removal the solubilized material shows many of the characteristics usually attributed to S1 receptors, such as high affinity for [3H]serotonin and its analogs and low affinity for serotonin antagonists.

Animals↗
PubMed1983

Hyperserotonemia and platelet serotonin uptake and release in schizophrenia and affective disorders.

The authors found that platelet serotonin concentrations were significantly elevated in patients with chronic schizophrenia and in patients with bipolar major depressive disorder. High-affinity serotonin uptake was significantly reduced only in patients with bipolar major depressive disorder. Thrombin-induced release of serotonin from platelets in any patient group was not different from that of normal control subjects. Platelet serotonin storage in chronic schizophrenic patients was also not different from that in normal control subjects. These platelet findings could not be explained by age, sex, or medication variables. The authors suggest that the pharmacodynamics of platelet serotonin may be different in chronic schizophrenia than in bipolar major depressive disorder.

Adult↗
PubMed1982

Genetic regulation of neurotransmitter enzymes and receptors: relationship to the inheritance of psychiatric disorders.

This report begins with a summary of the evidence for genetic involvement in certain major psychiatric syndromes. The relation of these disorders to deficits in central nervous system neurotransmitters is also summarized. These reviews serve as an introduction to our studies on the genetic regulation of neurotransmitters and their enzymes and receptors in inbred mice. The steady-state levels of the adrenal catecholamine biosynthetic enzymes are controlled genetically; not only is each enzyme regulated by a single locus, but also there is statistical evidence that the phenotypic expression of the entire pathway is regulated by a single gene. Studies on the biochemical mechanism of gene action suggest that genetic regulation is exerted on proteolysis of the enzymes, rather than their synthesis. In addition, we have examined the genetic control of dopamine receptors in inbred mice. Dopaminergic receptors in the nigrostriatal and mesolimbic pathways are under genetic control. Preliminary evidence suggests that the pathways are regulated by different genetic systems. If this early speculation proves true, it would have important clinical implications.

Animals↗
PubMed1982

Intrinsic and extrinsic determinants of neuronal development: relation to infantile autism.

This paper attempts to view the autistic syndrome in the context of a disorder of brain development. The authors review some of the known or suspected causes of the autistic syndrome: maternal rubella, metabolic diseases, and heredity. Some basic principles of cellular neuroanatomy and chemical neurotransmission are sketched. The stages of human brain development from neurulation through histogenesis, cell migration, and elaboration of dendritic trees and axonal projections are described. The authors conclude that there are a limited number of developmental loci that could be disrupted and lead to the autistic syndrome, and that these most probably occur in the end stages of neuronal development, after the migrating neurons have reached their final place in the brain and have begun to elaborate communicative processes. Finally, the authors speculate on how neurochemical disturbances might alter end stage neuronal differentiation leading to the pathology of infantile autism.

Autistic Disorder↗
PubMed1982

Effects of hypophysectomy and dexamethasone administration on central and peripheral S-adenosylmethionine levels.

The effects of hypophysectomy and dexamethasone administration on S-adenosylmethionine (SAM) levels in the adrenal, liver, pineal, and various brain regions were examined to determine the central and peripheral relationships between SAM and glucocorticoids in vivo. A simple and sensitive radioenzymatic assay was developed to measure tissue SAM concentrations following removal of its demethylated metabolite, S-adenosylhomocysteine (SAH), whose presence precludes accurate SAM determinations. Three patterns of SAM control emerged. In the adrenal, pineal, striatum, and midbrain, SAM levels fell after hypophysectomy and were restored by dexamethasone administration. In the thalamus, hypothalamus, hippocampus, and cerebellum, SAM levels increased after hypophysectomy and were not altered further by dexamethasone administration. In the liver, cortex, septum, and pons-medulla, SAM levels were not affected by either hypophysectomy or dexamethasone administration. These results suggest that multiple controls regulate SAM levels in vivo. The control factors are both highly tissue and region specific. While glucocorticoids are an important regulatory factor of SAM in some peripheral and CNS tissues, they are not the sole regulatory factor. In CNS regions where hypophysectomy increases SAM levels but glucocorticoid administration does not reverse the effects, other hypothalamic hormones, pituitary hormones, or neural factors may be involved in SAM regulation. Likewise, in regions where neither hypophysectomy nor glucocorticoid administration affects SAM levels, hypothalamic or neural factors may be involved even though pituitary factors do not appear to be important.

Adrenal Glands↗
PubMed1981

Dopamine receptor binding in inbred mice: strain differences in mesolimbic and nigrostriatal dopamine binding sites.

Dopamine receptors were examined by Scatchard analysis in the striatal and olfactory tubercle regions of 11 inbred mouse strains. Simultaneous determinations of the binding characteristics of 3H-labeled 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), a dopaminergic agonist, and [3H]spiroperidol, a dopaminergic antagonist, were examined. Among the 11 strains, the equilibrium dissociation constant (Kd) for agonist binding did not vary in either the striatum or the olfactory tubercle. Similarly, no strain differences were observed in the Kd for spiroperidol in either region, although the Kd for spiroperidol in the olfactory tubercle was uniformly higher than that in the striatum. Measurement of receptor concentrations revealed strain differences of up to 2-fold for both [3H]ADTN and [3H]spiroperidol binding sites. Within each brain region, the densities of agonist and antagonist binding sites correlated significantly. However, between brain regions there was no correlation in the density of agonist or antagonist binding sites, which suggests that mesolimbic and nigrostriatal dopamine neurons may be under independent genetic control. Analysis of [3H]spiroperidol displacement by clofluperol, aceperone, cinanserin, and mianserin in four inbred mouse strains revealed that 88-90% of the striatal spiroperidol sites are dopaminergic, with the remainder being serotonergic. In contrast, 53-66% of the olfactory tubercle [3H]spiroperidol binding sites are dopaminergic and 34-47% are serotonergic. These data suggest that genetic differences in serotonin receptors and dopamine receptors may exist among inbred mouse strains.

Animals↗
PubMed1981

Biochemical genetics of neurotransmitter enzymes and receptors: relationships to schizophrenia and other major psychiatric disorders.

Genetic control of catecholamine biosynthetic enzymes and dopamine receptors is described. The steady-state levels of each of the catecholamine biosynthetic enzymes in the adrenal is regulated by a single genetic locus. The entire biosynthetic pathway gives the appearance of concerted inheritance under the control of a single locus. Mesolimbic and nigrostriatal dopamine receptors are also genetically regulated. Preliminary evidence suggests that agonist binding sites differ from antagonist sites in both brain regions, and that the genetic controls, which are expressed on receptor site number, are independent in the two brain regions.

Adrenal Glands↗
PubMed1980

Interaction of opiate peptide and noradrenalin systems: light microscopic studies.

In this light microscopic immunocytochemical study beta-Endorphin (beta-END), leu-enkephalin and dopamine-beta hydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for beta-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between beta-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.

Animals↗
PubMed1980

Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control.

Rat pineal hydroxyindole-O-methyltransferase is controlled similarly to adrenal medullary phenylethanolamine N-methyltransferase. S-adenosylmethionine (SAM), the in vivo cofactor utilized by the enzyme to convert N-acetylserotonin to melatonin, protects this methyltransferase against tryptic proteolysis in vitro. Furthermore, in vivo studies suggest that the nucleoside itself is controlled by glucocorticoids. Hypophysectomy decreases hydroxyindole-O-methyltransferase levels as compared with control animals, while dexamethasone and SAM administration restore enzyme levels toward control values. In vitro proteolytic studies further demonstrate that, although N-acetylserotonin does not stabilize the enzyme against trypsinization, this substrate acts synergistically with SAM to confer greater stabilization than observed with SAM alone.

Acetylserotonin O-Methyltransferase↗