PubMed Health⌕ Search

Biomedical subjects

B J Morley

Publications and source records attributed to B J Morley.

At least 73 records · Page 4Linked to original sources
PubMed1986

Ganglionic nAChRs and high-affinity nicotinic binding sites are not equivalent.

High-affinity (Kd approximately equal to 10 nM) binding sites for nicotine and acetylcholine (ACh) have recently been identified in vertebrate brain. It has been suggested that these sites are desensitized ganglionic (C6) nicotinic acetylcholine receptors (nAChRs). We have tested the pheochromocytoma cell line PC12, which is known to contain well-expressed C6 nAChRs, to determine if these nAChRs are associated with high-affinity [3H]ACh-binding sites. We found that the high-affinity nicotinic [3H]ACh-binding site is absent in PC12 cells. We also found that the concentration of nicotine or ACh necessary to desensitize carbamylcholine-stimulated Na+ flux was at least two orders of magnitude greater than the concentrations used in binding experiments. We conclude that high-affinity nicotinic binding sites are not equivalent to C6 ganglionic receptors.

Acetylcholine↗
PubMed1986

Increases in the concentration of brain alpha-bungarotoxin binding sites induced by dietary choline are age-dependent.

We have previously reported that a diet supplemented with choline induces an increase in the concentration of a brain nicotinic-like receptor, as measured by alpha-bungarotoxin (BuTX) binding. Here we report the effects of choline administered in the drinking water on BuTX binding in the cortex, midbrain and brainstem of rats at 3 ages. In comparison with animals fed a choline-free diet, choline supplementation produced increases averaging 50% in 23-day-old rats and increases of approximately 30% in 60-day-old rats. Increases were also found in 6-month-old animals (averaging 16%), but the differences were generally not statistically significant. The mechanism responsible for the increase in the concentration of BuTX binding sites following the administration of dietary choline is not known, but the results are discussed in terms of choline as a precursor for the biosynthesis of acetylcholine and the biosynthesis of phospholipids. These data indicate that the administration of dietary choline is not likely to be effective in reversing cholinergic deficits by increasing the concentration of nicotinic-like receptors in aging rats.

Animals↗
PubMed1985

Purification and characterization of the alpha-bungarotoxin binding protein from rat brain.

The alpha-bungarotoxin (BGT) binding protein from rat brain has been purified and its polypeptide chain composition has been examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Polypeptide chains with Mrs of 55,000, 53,500 and 49,000 have been identified as constituents of the protein. The affinity ligand [3H]maleimidobenzyl trimethylammonium bromide ([3H]MBTA), used to identify the ligand binding site on neuromuscular junction acetylcholine receptors (NMJ AChRs), binds to the 55,000 dalton polypeptide chain. Using a technique where ligands are bound to the protein while the protein is immobilized on alpha-cobratoxin-Sepharose 4B, it was established that the brain BGT binding protein, like NMJ AChRs, possesses two binding sites for BGT. These experiments reinforce previous evidence that the brain BGT binding protein is closely related but not identical to NMJ AChRs.

Animals↗
PubMed1985

The development of somatostatin immunoreactivity in the interpeduncular nucleus of the cat.

Somatostatin (SS) immunoreactivity was localized in a population of neurons in the interpeduncular nucleus (IPN) of the developing and adult cat. SS-immunoreactive perikarya and fibers were found in several subdivisions of the IPN, but were most heavily concentrated in the central nucleus (IPC). Some immunoreactive fibers appeared to be associated with the ventral surface of the IPN where they may come in contact with the interpeduncular cistern. Bundles of immunoreactive fibers also appeared to leave the rostral pole of the IPN bilaterally. Still other SS-positive perikarya and fibers were associated with the tegmentopeduncular tract and the medial division of the dorsal tegmental nucleus. SS was present in both perikarya and fibers of the IPN at birth. The concentration of immunoreactivity increased dramatically during the first 100 days postnatal, but by 180 days the overall intensity of immunoreactivity had decreased to adult levels. These data indicate that SS may be present in the cat IPN in a specific population of neurons that is most active during early postnatal development. The data are consistent with previous suggestions that SS plays a special role in the development of certain neuronal systems and may be particularly important in the integration of behaviors during the neonatal period.

Animals↗
PubMed1985

The localization and origin of somatostatin-containing fibers in an auditory brainstem nucleus.

Immunoreactive perikarya and terminals have been visualized in the rat brainstem using antibodies raised against somatostatin 14 and somatostatin 28 (4-14) in a peroxidase antiperoxidase procedure. Labeling was observed in several areas of the brainstem, including the solitary nucleus, the dorsal lateral lemniscus, the ventral cochlear nucleus, several areas of the reticular formation, the nucleus of the spinal trigeminal tract, and the locus ceruleus. There was no obvious difference obtained with antisera against SS 14 and SS 28 (4-14). Several auditory areas were found to contain SS in discrete sub-groups of perikarya and terminals, suggesting the existence of one or more specific SS-containing auditory pathways. The origin of the SS-positive terminals in the medial nucleus of the trapezoid body was investigated using thermal and chemical lesions. It was concluded that these terminals originate from a specific SS-positive group of perikarya located either in or adjacent to the medial portion of the nucleus of the dorsal lateral lemniscus.

Animals↗
PubMed1985

Evidence that cell bodies in the arcuate nucleus of the hypothalamus are not cholinergic.

Central cholinergic pathways have been implicated in the control of pituitary hormone release. Based on studies using acetylcholinesterase (AChE) histochemistry, it has been proposed that the cholinergic neurons controlling hormone release originate in neurons of the arcuate nucleus (AH). Although AChE histochemistry has been widely utilized to map central cholinergic pathways, AChE is not an unequivocal marker for cholinergic neurons. A more precise method for determining that neurons are cholinergic is the immunocytochemical labeling of choline acetyltransferase (CAT). In order to determine if the AChE-positive neurons in the AH are cholinergic, we double-labeled tissue sections for CAT and AChE using a combined immunocytochemical and AChE-histochemical method. Although neurons in several areas of the brain could be labeled for both CAT and AChE, neurons in the AH were only AChE-positive. We concluded that the AChE-positive neurons in the AH may be cholinoceptive but are not likely to be the source of cholinergic neurons controlling hormone release from the pituitary gland.

Acetylcholinesterase↗
PubMed1984

The factor B and C2 genes.

Factor B and C2, components of the complement system, are novel types of serine proteinase that are encoded by genes in the major histocompatibility complex. cDNA probes specific for these two proteins have been used to isolate cosmid clones of genomic DNA which contain the Factor B and C2 genes. Southern blot analysis of the cosmid clones and of uncloned genomic DNA has shown that there are single Factor B and C2 loci that are less than 1 kilobase apart. The Factor B gene has been further characterized by DNA sequence analysis. It is approximately 6 kilobases in length, and is split into 18 exons. The amino acid sequence of the Ba fragment contains three homologous regions which are encoded by separate exons, suggesting that they arose by DNA duplication events. In the serine proteinase domain each of the functionally important parts of the active site are encoded on separate exons. Comparison of this region of the gene with the exon organization of other serine proteinases shows a close correlation between them, but also reveals the presence of an exon in Factor B with no homologous counterpart in the other serine proteinases. The possible functional significance of the peptide encoded by this exon and the evolution of this novel serine proteinase are discussed.

Amino Acid Sequence↗
PubMed1984

Internal homologies of the Ba fragment from human complement component Factor B, a class III MHC antigen.

The amino acid sequence of Ba, a fragment of the complement protein Factor B, has been determined from the sequence of its corresponding cDNA. Ba is composed of 234 amino acids and from the sequence two striking regions of internal homology are apparent which are related to a third less homologous region. Analysis of cloned genomic DNA using an 81-bp cDNA probe containing coding information for part of a leader peptide and nine amino acids at the N terminus of Ba has established the extent of the 5' end of the Factor B gene and shown that the region of the gene encoding Ba is approximately 1.6 kb in length.

Amino Acid Sequence↗
PubMed1983

Increase in hypothalamic nicotinic acetylcholine receptors in prepuberal female rats administered estrogen.

In previous studies, it has been reported that the administration of estrogen to prepuberal female rats produces precocious surges in the serum concentrations of luteinizing hormone (LH) and prolactin and the number of synaptic contacts in the arcuate nucleus. In the study reported here, we tested the hypothesis that the concentration of hypothalamic nicotinic acetylcholine receptors is the synaptic event initiating the precocious hormonal surges. A single injection of estrogen was administered to prepuberal female rats on day 25 and the serum concentrations of LH and prolactin and the concentration of the binding sites for alpha-bungarotoxin (BuTX), a putative nicotinic acetylcholine receptor ligand, were measured on day 27. The concentration of hypothalamic BuTX binding sites was increased by the estrogen treatment, but we found no evidence that this increase in receptors precedes or initiates the serum hormonal surges.

Animals↗
PubMed1983

Evidence that certain peripheral anti-acetylcholine receptor antibodies do not interact with brain BuTX binding sites.

The cross-reactivity of rat brain alpha-bungarotoxin (BuTX) binding sites with peripheral anti-acetylcholine receptor (nAChR) polyclonal and monoclonal antibodies was investigated in Triton extracts of several brain areas and purified whole brain putative receptors using radioimmunoassays and IgG/CNBr-Sepharose 4B immunoaffinity chromatography. The effects of the chronic intracerebral administration of antibodies on [125I]BuTX binding and food and water intake were also investigated. It was concluded that brain BuTX sites do not share antigenic determinants with peripheral nAChRs. Additionally, no evidence was found to support the suggestions that anti-nAChR antibodies affect food and water intake, or that chronic administration of antibodies alters [125I]BuTX binding in the hypothalamus of rats.

Animals↗
PubMed1983

Single-unit responses to cholinergic agents in the rat inferior colliculus.

Single units were recorded from the inferior colliculi of adult male rats anesthetized with urethane. Units were driven with tonal stimuli, and changes in unit responses to the tones were monitored during iontophoretic application of cholinergic drugs. The cholinergic agonists acetylcholine and carbamylcholine potentiated responses in about 50% and suppressed responses in about 35% of units tested. Cholinergic antagonists typically produced effects when delivered alone. Both d-tubocurarine and atropine methyl nitrate excited over 80% of units tested, while mecamylamine and scopolamine inhibited the majority of tested units. Dihydro-beta-erythroidine was generally ineffective. Alpha-bungarotoxin was generally ineffective when delivered alone, but blocked agonist effects. Post-stimulus time histogram (PSTH) patterns, response-intensity functions and response areas were examined for changes during drug delivery. Cholinergic agents did not differentially affect either time periods within the PSTH or frequency bands of response areas, but were especially effective for those intensities producing larger response rates. Taken together with evidence from biochemical studies, our results suggest the presence of a functional cholinergic input into the inferior colliculus which acts to modulate acoustic processing.

Animals↗
PubMed1981

Ontogeny of gamma-hydroxybutyric acid. I. Regional concentration in developing rat, monkey and human brain.

Steady state levels of gamma-hydroxybutyrate (GHB) were measured in whole brain and discrete regions of brain in developing and adult rat, monkey, and human brain. Postmortem changes in concentration of GHB in rat and human brain were also assessed. There were no significant postmortem changes in GHB under the conditions which the ontogeny experiments were done. The concentration of GHB was uniformly higher in the immature brains of the 3 species studied. In the rat the highest concentration was in immature hypothalamus and cortex with a significant decrease occurring between postnatal day 12 and 14. In human, the highest concentration was in fetal cerebellum and adult hypothalamus. Comparison of these data with published ontogeny data for gamma-aminobutyric acid (GABA) suggest that there may be a source of GHB in brain other than GABA.

Adolescent↗
PubMed1980

Juvenile myasthenia gravis.

We studied 32 children with myasthenia gravis over a period of 12 years. The mean age at onset was 7.7 years. Presentation was ocular in 63% of patients. Another major disease in addition to myasthenia occurred in 44% of patients; a seizure disorder was the most commonly associated disease. Serum IgG antibody to nicotinic acetylcholine receptor was present in 53% of patients and did not correlate with severity of disease or treatment. Medical management was effective in 63%; thymectomy was effective in only 28%. We conclude that myasthenia gravis appears commonly before age 10 and is associated with the risk of some disease other than hyperthyroidism. Serum IgG nicotinic acetylcholine receptor antibody is present less frequently than in normal adults, and vigorous medical management should be attempted before thymectomy.

Adolescent↗