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Biomedical subjects

L L Iversen

Publications and source records attributed to L L Iversen.

At least 73 records · Page 4Linked to original sources
PubMed1984

Vasopressin, oxytocin and neurophysins in the human brain and spinal cord.

The concentrations of arginine vasopressin, oxytocin, and their related neurophysins were compared in many areas of postmortem human brain and spinal cord using specific radioimmunoassays. In the hypothalamus the ratio of vasopressin to oxytocin was approximately 3:1, and in the extrahypothalamic areas of the brain the greatest amount of both peptides was present in the locus coeruleus, and to a lesser extent the periaqueductal grey. Vasopressin only was found in the substantia nigra, and globus pallidus. In the medulla, including the nucleus of the solitary tract, the dorsal nucleus of the vagus, and the nucleus of the spinal tract of the trigeminal nerve, the amount of oxytocin was greater than that of vasopressin. In the spinal cord oxytocin predominated over vasopressin to an even greater extent, and reached particularly high values in certain segments of the intermediolateral grey column and dorsal horn. Estrogen-stimulated and nicotine-stimulated neurophysins (ESN and NSN) were both found in large amounts in those areas of the brain and spinal cord where the concentrations of the nonapeptides were greatest, but when the molar ratios of ESN to oxytocin and NSN to vasopressin were compared there was an excess of ESN.

Adult↗
PubMed1984

3H-substance P binding to guinea-pig ileum longitudinal smooth muscle membranes.

Specific binding of 3H-substance P was studied in guinea-pig ileum longitudinal smooth muscle membranes. A single population of non-interacting sites with an apparent dissociation constant of 1.8 nM was observed. The relative potencies of some structural analogues of substance P, notably eledoisin and substance P (5-11), in competing for 3H-substance P binding sites, however, had little resemblance to their potencies in contracting the intact muscle or in eliciting the breakdown of inositol phospholipids in this tissue. The results are discussed in the light of other binding studies for substance P.

Animals↗
PubMed1984

Correlation of cortical cholinergic and GABA deficits with quantitative neuropathological findings in senile dementia.

The present paper examines the relationship between choline acetyltransferase (ChAT) activity and gamma aminobutyric acid (GABA) concentrations with neuronal counts, senile plaque counts and estimates of neurofibrillary tangles in a series of 25 cases of senile dementia of Alzheimer type (SDAT) with appropriate controls. ChAT activity was significantly positively correlated with neuronal counts in the frontal and temporal region for the whole group but not in the demented or control subgroups. Significant negative correlations were also found between plaque counts and ChAT activity in all areas studied in the total group of subjects and in most of the SDAT groups. Significant negative correlations between ChAT activity and estimates of neurofibrillary change occurred in the frontal area and midtemporal gyrus in the SDAT cases. All the above correlations were seen most prominently in the youngest dementia patients (less than 79 years of age) who exhibited the most severe neuropathological and neurochemical deficits. The neurochemical distinction between the young and elderly age group of SDAT cases was well illustrated by the paradoxical trends of significantly increased GABA and ChAT levels with increasing age. The few significant correlations observed between GABA and cell counts were positive and occurred in the temporal lobe in the younger age group. Plaque counts and neurofibrillary tangle estimates showed little correlation with GABA concentrations.

Alzheimer Disease↗
PubMed1984

Evidence for multiple muscarinic receptor subtypes in human brain.

Pirenzepine, a compound with selective antimuscarinic activity, was used to distinguish muscarinic acetylcholine receptor subtypes in normal human brain. Hill coefficients and IC50 values derived from the inhibition of specific [3H]L-quinuclidinyl benzilate receptor binding suggest the presence of two muscarinic binding sites, differing both in affinity for pirenzepine and in tissue distribution.

Amygdala↗
PubMed1983

Loss of pigmented dopamine-beta-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type.

Serial sections of human brainstem were used to determine the total number of pigmented cells in locus coeruleus and, by immunohistochemical staining using an antiserum directed against human dopamine-beta-hydroxylase (DBH), the number of DBH-positive cells. In 12 brains from elderly control and dementia subjects there wer not significant differences in the total cell populations determined in the same brain by the two techniques. In 6 patients with senile dementia of Alzheimer's type there was a variable loss (average about 60% reduction) in locus coeruleus cells when compared to controls of similar age. The loss of noradrenergic neurones from locus coeruleus was accompanied by an average reduction of similar magnitude in noradrenaline concentration in temporal cortex, with no change or an increase in dopamine content. There was also a significant reduction in the cholinergic marker choline acetyltransferase in cortex samples from the dementia cases.

Aged↗
PubMed1983

Tissue selectivity of substance P alkyl esters: suggesting multiple receptors.

Previous studies from this laboratory suggested that two subtypes of substance P receptor may exist, based on the observations that substance P and related peptides did not exhibit complete cross-desensitisation on guinea-pig ileum, and that two distinct rank orders of potency of tachykinins were observed in various test systems. The present study has added support to this hypothesis by extending the screening of tachykinins to further bioassays and by testing novel analogues. In particular, C-terminal alkyl esters of substance P were found to exhibit a high degree of selectivity to one putative receptor subtype. The synthesis of the alkyl esters by esterification of substance P free acid is described.

Animals↗
PubMed1983

Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action.

It is well established that neuroleptic drugs are antagonists of brain dopamine receptors. The role of the reported increase in dopamine receptors (measured as 3H-spiperone binding sites) in post-mortem brain tissue from patients with schizophrenia in the aetiology of the disease is, however, unclear. We have found this increase only in chronically neuroleptic-treated patients, indicating that the increase is probably due to this neuroleptic treatment. Many neuroleptic drugs have a high affinity for a subgroup of 5-hydroxytryptamine receptors, which have also been implicated in schizophrenia. Using the specific ligand 3H-ketanserin, we find that certain neuroleptics have a higher affinity for these 5-HT2 receptors than for the dopamine D2 site. Although changes in these receptors have been reported in schizophrenic brain tissue we have been unable to find any difference in receptor density in cortical tissue from schizophrenics and control subjects.

Antipsychotic Agents↗
PubMed1983

Dose-dependent effects of capsaicin on primary sensory neurons in the neonatal rat.

The numbers of myelinated and unmyelinated fibers were counted in dorsal roots of adult rats treated neonatally with capsaicin in doses ranging from 5 to 100 mg/kg. Substance P and somatostatin levels in the spinal cord, dorsal roots, and sensory ganglia also were determined in control and treated animals. Capsaicin administration lead to the loss of both small myelinated and unmyelinated fibers from dorsal roots. However, whereas a near total loss, up to 94%, of unmyelinated fibers was achieved after high doses of capsaicin, the reduction of myelinated fibers, even of the smallest caliber, did not exceed 40%. The degree of fiber loss showed a clear dose dependency, with little detectable damage to myelinated fibers at doses of less than 50 mg/kg and with an ED50 for damage to unmyelinated fibers of 5 to 10 mg/kg. In all of the structures examined, particularly the dorsal roots, a roughly parallel decrease of substance P and somatostatin was found with capsaicin dose. The depletions of spinal cord substance P (55%) and somatostatin (20%) produced by neonatal capsaicin treatment were similar to those produced by dorsal rhizotomy. Capsaicin does not appear to be specific for primary afferents containing either substance P or somatostatin.

Animals↗
PubMed1982

Extrahypothalamic vasopressin is unchanged in Parkinson's disease and Huntington's disease.

Vasopressin immunoreactivity was measured post-mortem in the locus coeruleus and substantia nigra of 16 cases of Parkinson's disease and multisystem atrophy, 10 cases of Huntington's chorea and 28 normal controls. Amounts of vasopressin did not differ significantly (P greater than 0.05) between the 3 groups. Immunohistochemistry demonstrated vasopressin within nerve terminals. These data are consistent with an extrinsic vasopressin system in the human locus coeruleus and substantia nigra.

Adult↗
PubMed1982

Endogenous GABA release from slices of rat cerebral cortex and hippocampus in vitro.

Using a rapid, simple and sensitive radioreceptor assay, a Ca2+-dependent K+-evoked release of endogenous GABA was demonstrated from rat cortical and hippocampal slices in vitro. This evoked-release of endogenous GABA was similar to that of [3H]GABA release (in its Ca2+ dependency) but differed from the latter in having a higher signal to noise level. Neither 5-HT nor a stable enkephalin analogue had any effect on endogenous GABA release from hippocampus slices.

Animals↗
PubMed1982

The substantia innominata in Alzheimer's disease: an histochemical and biochemical study of cholinergic marker enzymes.

Acetylcholinesterase staining was examined in the substantia innominata of 3 normal human brains. Large intensely stained neurones were seen within the region of the basal nucleus of Meynert which is believed to be the origin of the cholinergic projection to the neocortex in animals. On the basis of the acetylcholinesterase staining pattern, the substantia innominata was dissected from post-mortem brain tissue of 19 cases of Alzheimer's disease (AD) and 16 controls so as to include the basal nucleus. Choline acetyltransferase (ChAT) activity was found to be reduced in the substantia innominata and amygdala in AD but not in the adjacent lentiform nucleus and hypothalamus.

Acetylcholinesterase↗
PubMed1982

Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions.

A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.

Animals↗