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Biomedical subjects

L L Iversen

Publications and source records attributed to L L Iversen.

At least 91 records · Page 5Linked to original sources
PubMed1982

Increased brain dopamine and dopamine receptors in schizophrenia.

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Adolescent↗
PubMed1982

Substance P receptors in the nervous system and possible receptor subtypes.

The ability of various related peptides and substance P analogues to compete for the binding of 3H-labelled substance P to rat brain membranes corresponds with their known biological activities, providing a simple model for studies of peptide receptors in the central nervous system. In salivary gland and brain slices substance P and related peptides stimulate the rate of incorporation of phosphatidylinositol, offering an alternative biochemical model for substance P receptor studies. Two types of receptor may be responsible for the actions of substance P on peripheral tissues: the SP-P type, where all tachykinins are approximately equally active, and the SP-E type, where eledoisin and kassinin are more potent than the other tachykinins. Alkyl esters of substance P appear to act as selective SP-P agonists.

Animals↗
PubMed1982

The possible existence of multiple receptors for substance P.

1. The possible existence of multiple receptors for substance P (SP) was investigated by examining the relative pharmacological potencies of SP and related peptides in contracting guinea pig ileum, in potentiating electrically evoked contractions of rat vas deferens preparations and in competing for 3H-SP receptor binding in rat brain membranes, and by comparing the extent of cross-tachyphylaxis of various analogues with SP in the guinea pig ileum. 2. Different rank orders of potencies were observed among SP, its C-terminal fragments, analogues and related tachykinins in the different test systems, and these could not be explained by differential access to the target organ receptors. 3. In contrast to SP and physalaemin, both eledoisin and a metabolically stable SP analogue, [pGlu5, MePhe8, Sar9]-SP5-11 exhibited differential recovery from SP tachyphylaxis in the guinea pig ileum, and part of their spasmogenic action in this preparation was atropine-sensitive. 4. The results suggest the possible existence of multiple SP receptors, and the specificity of those in the brain may be different from those in the gut. The structural and pharmacological basis for subdividing tachykinins into SP-physalaemin and eledoisin-kassinin families is also discussed.

Animals↗
PubMed1982

Substance P.

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Animals↗
PubMed1982

Tritiated peptides. 12. Synthesis and biological activity of [4-3H-Phe8]substance P.

Substance P has been prepared 3H labeled at Phe8 by catalytic deiodination of a protected precursor. Synthesis of the precursor was by solid-phase methodology on polydimethylacrylamide resin and by condensation in solution of fragments covering sequences 1-4, 5-7, and 8-11. Free peptide made by each route analyzed satisfactorily and had the same chromatographic characteristics as unlabeled substance P. It was indistinguishable from the latter by radioimmunoassay when N and C terminally directed antisera were used and in the ability to cause contractions of isolated guinea pig ileum. Specific radioactivity was 23 Ci/mmol.

Amino Acids↗
PubMed1982

A post-mortem study of the cholinergic and GABA systems in senile dementia.

Choline acetyltransferase (ChAT) activity and gamma-aminobutyric acid (GABA) concentration were measured in 19 cerebral cortical areas and 22 subcortical areas of brains from 26 control and 25 histologically proven cases of Alzheimer's disease. Reduced ChAt activity was observed in all the cortical areas examined in the Alzheimer cases dying before the median age of 79 years. In the Alzheimer cases aged greater than 79 years at death, 7 out of the 9 frontal cortical areas had a normal ChAT activity when compared with controls. Significant reductions in GABA concentrations in the Alzheimer cases were confined to the temporal cortex. Significant reductions in ChAT activity in subcortical areas were confined to 8 of the 22 regions examined. Notably these included the septal nuclei and substantia innominata, the proposed origins of the cholinergic projections to the hippocampus and neocortex, respectively. There were no reductions in GABA concentrations outside the cerebral cortex. Four multi-infarct cases and 6 cases with normal histology were found to have a small reduction in ChAT activity confined to only a few areas. The data are consistent with a predominant loss in Alzheimer's disease of the diffuse cholinergic projection from the brainstem and basal forebrain.

Aged↗
PubMed1982

Substance P.

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Central Nervous System↗
PubMed1982

Regional distribution of neurotensin in human brain.

Neurotensin (NT) is an endogenous neuropeptide that is active in many preclinical screening tests for neuroleptic drugs. Using a radioimmunoassay, we have studied the regional distribution of NT in postmortem human brain and in cerebrospinal fluid. Highest levels were present in the hypothalamus, substantia nigra, and limbic areas, whereas much lower amounts were found in the cortex and striatum. The chromatographic properties of hypothalamic immunoreactivity on ion-exchange and high pressure liquid chromatography were similar to those of the synthetic tridecapeptide. We conclude that NT is present in human brain with a distribution resembling that seen in other species, such as rat and monkey.

Adult↗
PubMed1982

Effects of opiates and osmotic stimuli on rat neurohypophyseal metabolic activity monitored with [3H]-2-deoxyglucose.

The metabolic activity of the neural lobe of the rat pituitary gland was measured by autoradiographic estimation of the rate of accumulation of 1-[3H]-2-deoxy-D-glucose ( [3H]-2DG). Replacement of drinking water by 2% saline for 5 days resulted in a 300% increase in [3H]-2DG accumulation in the neural lobe. Morphine (8 mg/kg s.c.) increased [3H]-2DG uptake by 213%, and this effect was antagonized by naloxone. Morphine-tolerant rats also showed an increased uptake of [3H]-2DG, and morphine actually reduced the neural lobe activity in these animals. Rats with monosodium glutamate induced lesions of the circumventricular organs no longer showed any increase in neural lobe activity after morphine. Homozygous Brattleboro rats on an ad libitum water intake showed greater neural lobe activity than normal controls, and replacement of drinking water with 2% saline for 24 h resulted in a massive increase in [3H]-2DG uptake. In none of these studies was any alteration detected in the metabolic activity of the supraoptic or paraventricular nuclei.

Animals↗
PubMed1982

Dopamine and [D-ALA2, D-Leu5]enkephalin inhibit the electrically stimulated neurohypophyseal release of vasopressin in vitro: evidence for calcium-dependent opiate action.

The effects of both dopamine and enkephalin agonists were assessed on electrically stimulated vasopressin secretion from the isolated neural lobe. Both dopamine (10(-6) M) and the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene; 10(-6) M) significantly reduced the stimulated release of vasopressin. This reduction in vasopressin secretion was prevented by the dopamine antagonist sulpiride (10(-6) M). [D-Ala2, D-Leu5]Enkephalin (DADLE) also inhibited vasopressin release and its effect was additive to that of ADTN. The effect of DADLE was prevented by the opiate antagonist naloxone and was also sensitive to the calcium content of the medium. Low calcium concentrations markedly increased the inhibitory effect of DADLE, while high concentrations abolished its effect. These findings provide evidence of a direct inhibitory action of both dopamine and enkephalins at the level of the neural lobe and suggest that the effect of enkephalins may be intimately related to calcium-sensitive neurosecretory events.

Animals↗
PubMed1981

3-mercaptopropionic acid inhibits GABA release from rat brain slices in vitro.

3-Mercaptopropionic acid (3MP) (1 mM) inhibited the potassium-evoked release of endogenous GABA from slices of rat hippocampus and cerebral cortex in vitro. This did not appear to be due to an inhibition of GABA biosynthesis, since 3MP failed to affect the basal rate of GABA release or to accelerate the decline in the GABA content of tissue slices during prolonged exposure to 3MP (up to 120 min). 3MP, furthermore, inhibited the potassium-evoked release of [3H]GABA from preloaded brain slices, suggesting a direct inhibitory effect on GABA release. The threshold concentration was approximately 0.1 mM. 3MP at 1 mM failed to inhibit the potassium-evoked release of [3H]5-hydroxytryptamine, [3H]noradrenaline or somatostatin under similar conditions. The ability of 3MP to inhibit GABA release may contribute to the convulsant properties of this substance in vivo.

3-Mercaptopropionic Acid↗
PubMed1981

6 -Hydroxydopamine decreases benzodiazepine but not GABA receptor binding in rat cerebellum.

The noradrenergic innervation to the cerebellum was lesioned by intracerebroventricular 6-hydroxydopamine and the effects on GABA and benzodiazepine receptors followed by radiolabelling experiments. This lesion produced a 20% decrease in benzodiazepine receptor labelling in the cerebellum with no change in the labelling of GABA receptors. This provides further evidence for a lack of identity between the GABA and benzodiazepine receptors.

Animals↗
PubMed1981

Chromatographic behaviour and post-mortem stability of somatostatin in the rat and mouse brain.

Somatostatin-like immunoreactivity (SSLI) extracted from mouse and rat brains was found to be homogeneous and identical to authentic somatostatin (SS) in its chromatographic behaviour on reverse-phase high-performance liquid chromatography (HPLC). SSLI was found to be stable in mouse brain stored under post-mortem conditions simulating the handling of human autopsy material for up to 72 h. However, the amount of SSLI extractable by acetone-HCl was found to decrease over the first 10 h of post-mortem storage to about 25% of the control level, hence care must be exercised in choosing an appropriate extraction method for SSLI measurements in post-mortem brains.

Animals↗
PubMed1981

Release of somatostatin from extra-hypothalamic rat brain slices: inhibition by dopamine and morphine.

Calcium-dependent potassium-evoked release of somatostatin-like immuno-reactivity (SSLI) and preloaded [3H]noradrenaline ([3H]NA) could be demonstrated simultaneously from slices of rat cerebral cortex, globus pallidus and trigeminal nucleus. The release of [3H]NA from cortical slices differed from that of somatostatin (SS) in its K+-dependency, with the release of SS having a higher threshold. Both morphine (10 microM) and dopamine (50 microM) significantly inhibited the potassium-evoked release of SS from the cerebral cortex, without affecting its basal release. The effect of morphine was naloxone reversible.

Animals↗