Cholecystokinin peptides and receptor binding in rat brain after DSP-4 treatment.

The neurotoxin DSP-4 has, in this laboratory, previously been shown to upregulate cholecystokinin (CCK) binding in the frontal cortex and the hippocampus in rats. The present study investigated the effect of DSP-4 on CCK peptide levels and CCK receptor binding in some rat brain areas. Sprague-Dawley rats were given single injections of DSP-4 (10 and 50 mg/kg) and examined after 1 week. Wistar rats were given an injection of DSP-4 (50 mg/kg) and evaluated 1 week and 4 months after treatment. No significant changes in CCK levels or in CCK binding were found. It has been found that stress produced by handling of the rats immediately before decapitation can result in an increase in cortical CCK receptor binding. This finding led to the speculation that the upregulation of CCK binding after DSP-4 treatment which was reported earlier, reflects a stress-potentiating effect of DSP-4.

Cholecystokinin in CSF from depressed patients: possible relations to severity of depression and suicidal behaviour.

Levels of cholecystokinin (CCK) peptides were measured in the CSF from 105 patients suffering from major depressive disorders admitted to a research psychiatric ward for diagnostic evaluation, by a radioimmunoassay method using two different antibodies. Relations between CCK levels and parameters of depression, anxiety, and suicidal behaviour were investigated. Significant inverse correlations were found between CCK levels and certain depression and anxiety parameters. Patients who had made one or more suicide attempts tended to have higher CSF CCK levels than those who had not. No correlations were found between CSF CCK and 5-HIAA or HVA, or with plasma cortisol.

Brain ATP:L-methionine S-adenosyltransferase (MAT), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH): regional distribution and age-related changes.

The distribution of the activity of the enzyme methionine adenosyltransferase (ATP:L-methionine S-adenosyltransferase, EC 2.5.1.6, MAT) was investigated in human postmortem brains of individuals without a known history of neuropsychiatric disorders. The brain regions were the frontal, temporal, parietal and occipital cortices, nucleus caudatus, putamen, globus pallidus, thalamus and white matter. The activities in the nucleus caudatus and putamen were approximately 25% higher than the activities in the seven other brain regions, however, not on a statistically significant level. The apparent values of MAT Km and Vmax in the parietal cortex were 11.41 +/- 3.51 microM methionine and 25.72 +/- 3.90 nmol/mg protein/h, respectively. In the frontal cortex, a significant positive correlation between age and the activity of MAT was found (r = 0.997, P < 0.01). Concerning MAT stability in the rat brain, there was a steady decrease in the activity with postmortem time in the brains kept for 0-72 h at room temperature (23 degrees C), which reached the level of significance at 24 h. The activity did not change significantly when the brains were kept for 120 h at 4 degrees C, or by freezing and thawing the tissue before analysis. In a parallel study in rats of different ages (2-22 months), a homogeneous distribution of SAM and SAH was observed in the cortex, striatum, midbrain, hypothalamus, brainstem and cerebellum. The lowest levels of SAM and the highest levels of SAH observed in the striatum gave the lowest SAM/SAH ratio. The SAH content of rat cerebral cortex was highest in the oldest group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin peptides and receptors in the rat brain during stress.

Cholecystokinin (CCK) has been implicated in stress and anxiety disorders. We have studied the levels of different molecular forms of CCK and CCK receptor characteristics in rats kept for 1 h in individual cages and exposed to decapitation of conspecifics, and a control group which was decapitated immediately. Total CCK concentration was found to be increased in the hippocampus of stressed animals in the first experiment: this finding was not confirmed in further studies. No effect of stress was found on total CCK levels in the frontal cortex, hypothalamus, striatum, and septum. CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, and CCK-4 were separated by HPLC and measured with two antibodies with different selectivity: no effect of stress was found on the levels of any of these molecular forms of CCK. Injection procedure and diazepam (5 mg/kg) administration had no effect on total CCK levels. Exposition of rats to the decapitation procedure increased [3H]-CCK-8 binding in the frontal and cerebral (whole-frontal) cortex. This effect could not be blocked by diazepam pretreatment. Injection procedure itself increased CCK receptor binding in the cerebral cortex, but the effect of this type of stress was smaller in magnitude. The upregulation of CCK receptors in stressed animals was due to the increased binding of radioligand on CCKB receptor subtype.

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment.

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCKB receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt's swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCKB receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCKB receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found.

Factors associated with divorce in intrafamily child sexual abuse cases.

This study analyzes factors related to the decision to divorce in intrafamilial sexual abuse cases. Data was collected on 128 cases of incest in St. Louis, Missouri, through the Washington University Child Guidance Center. Examination of multiple variables revealed there are differences between child sexual abuse cases that elect to stay together vs. those that divorce subsequent to the discovery of abuse. Families that broke up were more likely to have young child victims and have additional problems with domestic violence. The child was more likely to have revealed the abuse to the mother and have been believed by her in divorcing cases.

Reversal of glucose-induced inhibition of insulin release by dibutyryl cyclic AMP.

Insulin release in response to glucose was measured after culture of islets from ob/obmice in a medium deficient in Ca2+. When present at a concentration of 6 mmol/l, glucose inhibited, insulin release. After activation of the alpha2-adrenergic receptors by 1 mumol/l clonidine also 20 mmol/l glucose became inhibitory. The inhibitory action of glucose on insulin release disappeared in the presence of 1 mmol/l dibutyryl cyclic AMP. Raising the glucose concentration from 3 to 20 mmol/l resulted in increased cytoplasmic Ca2+ after an initial depression. Whereas clonidine removed the Ca2+ increase, this phase was partly restored after simultaneous addition of dibutyryl cyclic AMP. It is concluded that cyclic AMP plays a major role in controlling the balance between the stimulatory and inhibitory components in the glucose action on insulin release.

Cholecystokinin peptides and receptor binding in Alzheimer's disease.

Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in high concentrations and is involved in learning and memory as well as neurodegenerative processes. Cortical brain samples from 9 patients with Alzheimer's disease and 9 matched control cases were studied with respect to the concentrations of various molecular forms of CCK and the CCK receptor binding characteristics. No differences were found between patients and controls in any of these measures. Significant correlations were found between the concentrations of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition, the concentrations of CCK-4 and CCK-5 showed a highly significant and positive correlation.

Transmethylation reactions and autoradiographic distribution of vitamin B12: effects of clioquinol treatment in mice.

The catastrophic epidemic of subacute myelo-optic neuropathy (SMON) affected Japan around 1970 with thousands of victims. The cause was attributed to high doses of locally acting oxyquinolines. It has been speculated that oxyquinoline derivatives of the clioquinol type can disturb the retention of vitamin B12 through chelation of Co2+. In the present paper, possible effects of clioquinol on the uptake and tissue distribution of [57Co]-cyanocobalamin have been studied in mice. In vivo experiments showed markedly decreased accumulation of radiolabelled vitamin B12 in the kidney and skin in animals that were pre-treated with clioquinol. The chloroform:water partition coefficients for [57Co]-cyanocobalamin in the presence or absence of clioquinol were also determined. No statistically significant alterations in the partition coefficient for [57Co]-cyanocobalamin in the presence of clioquinol was evident, indicating that clioquinol does not bind cobalt. In addition, transmethylation reactions in the CNS in mice treated with clioquinol were studied. Specific activities of methionine adenosyltransferase, and S-adenosylhomocysteine levels were not affected. In contrast, clioquinol treatment caused a significant increase in the levels of S-adenosylmethionine in the brain. The data of the present study show that clioquinol treatment can affect the accumulation of vitamin B12 in the kidney and the skin but not in the brain. These results do not support the hypothesis that clioquinol causes its damage to the nervous system by a direct chemical interaction with vitamin B12.

Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson's disease.

In the present study, levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in whole blood as well as L-methionine S-adenosyltransferase (MAT) activity in erythrocytes were assayed in a series of 20 patients with Parkinson's disease and 12 healthy control subjects. A significant difference was found with regard to SAM levels between patients and controls, with the detected levels being 383.1 +/- 41.5 nM for the parkinsonian patients and 680.6 +/- 30.9 nM for the controls. With regard to SAH, we found no difference between the groups. The catalytic activity of MAT was increased by 30% in patients compared to controls, with the Vmax for methionine being 17.9 +/- 3.7 and 13.9 +/- 2.2 pmol/mg/h, respectively.