Actin-binding protein is a component of bovine erythrocytes.

Actin-binding protein (ABP) is a well-characterized polypeptide capable of crosslinking filamentous actin. To date, this polypeptide has been shown to exist in a number of tissues and cultured cell lines. This report shows that by using a panel of three monoclonal antibodies for immunoblotting and immunofluorescence analysis, that ABP is present in bovine erythrocytes. Moreover, the data obtained suggest that this protein is a component of the erythrocyte membrane skeleton. Additionally, bovine erythrocyte ABP is shown to possess both an apparent molecular weight and an isoelectric point identical to that of bovine smooth muscle filamin, implying that these two polypeptides are identical.

Effects of nicotine and nicotine/ethanol on human placental amino acids transfer.

Ethanol abuse and smoking during pregnancy both result in decreased offspring weight. One explanation for this may be impaired placental nutrient transport. This study assessed this possibility utilizing the 4-hr perfused human placental system and human placental vesicles exposed to "physiological," 0.2 microM and large (about 20 microM) nicotine concentrations alone, as well as nicotine combined with ethanol, 200 or 400 mg/ml, for up to 48 hr. Two nonmetabolizable amino acids, alpha-aminoisobutyric acid (AIB) and cycloleucine (CLEU) were used as probes. Nicotine was measured by gas chromatography in the placental perfusion system and vesicles and verified as to concentration. There was no statistically significant evidence of decreased transport of these amino acids with exposure to nicotine alone or nicotine and ethanol together in either test system. Thus, brief exposure to nicotine and ethanol does not impair amino acid transport by the human placenta.

Effect of ethanol on human placental transport of model amino acids and glucose.

Prior studies in rodents, sheep, and subhuman primates have shown that ethanol, especially after chronic exposure, inhibits the transport of amino acids by the placenta. A small decrease in glucose transport by rat placenta chronically exposed to ethanol has also been noted. With human placental slices, however, only pharmacological (high) concentrations of ethanol impaired uptake of amino acids, and there are no data on glucose transport. In the present study, the effect of brief exposure to ethanol on human placental transport of model amino acids and glucose was studied by two techniques not previously jointly employed for this--the perfused human placental cotyledon and human placental vesicle systems. The nonmetabolizable amino acids, alpha-aminoisobutyric (AIB) acid and cycloleucine (CLEU), as well as D-glucose, and nonmetabolized glucose (3-O-methyl-D-glucose), were used as probes. AIB and CLEU are transferred normally by active transport and D-glucose by facilitated transport from maternal to fetal compartments. The perfused placental system was exposed to ethanol (300-500 mg%) for 2-4 hr and the vesicles to 200-400 mg% ethanol for times varying from 10 min to 48 hr. There was no impairment of AIB, D-glucose, or 3-O-methyl-D-glucose transfer by ethanol using these techniques. Normally, about 60% of AIB transport by human placenta is sodium dependent. This component (using the vesicle system) was also not impaired by ethanol. Ethanol caused a very small decrease of CLEU clearance by the perfused human placenta (p = 0.05) but not using vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian hormone secretory profiles in women with severe premenstrual tension syndrome.

The circadian secretory profiles of serum prolactin, growth hormone and cortisol were measured in two women suffering from severe premenstrual tension syndrome and in two asymptomatic control subjects. Subjects and controls were screened and included after a rigorous selection process. Blood samples were obtained every 30 min over a period of 24 h in each woman both on day 9 (follicular phase) and day 26 (luteal phase) of the menstrual cycle. There was no relationship between the hormonal secretory profiles and the premenstrual tension syndrome.

Plasma prolactin and severe premenstrual tension.

It has been suggested that elevated luteal phase prolactin (PRL) levels may have an important role in causing some of the symptoms of the premenstrual tension syndrome (PMTS). Thirty-seven women suffering from severe premenstrual dysphoria were selected for this study. Single morning and afternoon serum PRL evaluations were performed during the follicular (day 9) and late luteal (day 26) phases of the menstrual cycle. PRL was measured by an established double antibody radioimmunoassay technique. All mean PRL values were within the normal range. Only afternoon mean PRL levels showed a tendency for a premenstrual increase. The significance of this statistical finding is unclear, since one-third of the subjects showed a decrease in premenstrual PRL levels. Twenty-four hour PRL secretory profiles recorded on days 9 and 26 in two women with extremely severe PMTS and in two asymptomatic matched control subjects also failed to show a significant correlation between PRL levels and PMTS. Thirty subjects participated in a treatment trial using bromocriptine. A marked rebound hyperprolactinemia was observed in a subgroup of women nine days after cessation of bromocriptine. This was associated with no detectable effect on mood, behavior, or menstrual regularity. Thus, our data fail to show any specific relationship between PRL and PMTS.

CCK receptors and human neurological disease.

Cholecystokinin (CCK) receptor binding was measured in postmortem brain tissue of patients with Alzheimer's dementia, Huntington's chorea, and neurologically healthy matched controls. CCK binding was significantly reduced inthe basal ganglia and cerebral cortex of Huntington's patients, but was normal in the temporal and cingulate cortex of patients with Alzheimer's disease. These findings indicate that CCK receptor loss is unique to specific neurodegenerative disease(s), and that CCK may be involved in the symptoms of Huntington's disease but is not implicated in the neuropathology of Alzheimer's dementia.

Cholecystokinin receptors are decreased in basal ganglia and cerebral cortex of Huntington's disease.

Cholecystokinin (CCK) receptors were found to be significantly reduced in basal ganglia and cerebral cortex of post-mortem from Huntington's patients with matched controls. The magnitude of the reduction in CCK binding (69% in basal ganglia, 43% in cerebral cortex) is consistent with the degree of neuronal degeneration in basal ganglia, but suggests a possibly selective loss of CCK receptor-containing neurons in cerebral cortex of Huntington's patients.

Localization of cholecystokinin receptors on neuronal elements in rat caudate nucleus.

Various chemical and physical lesions were employed to elucidate the cellular localization of cholecystokinin (CCK) receptors in the rat caudate nucleus. A wide knife cut severing all caudal afferents reduced caudate CCK receptors by approximately 25%, indicating that some receptors lie on axons and (or) terminals of neurons originating outside of the caudate. However, most CCK receptors appear to be located on neuronal cell bodies intrinsic to the caudate nucleus, since local injections of kainic acid reduced caudate CCK receptors by approximately 75%. These findings are similar to recent data from our laboratory on the concentration of CCK receptors in the basal ganglia of patients with Huntington's disease, and suggest that CCK may be involved in the regulation of extrapyramidal motor function.

Postnatal ontogeny of cholecystokinin receptors in rat brain.

The postnatal ontogeny of cholecystokinin receptors and cholecystokinin was determined in rat brain. The binding of cholecystokinin (CCK) to rat forebrain receptors was very low at 1-2 days of age, rose to a maximum at 12 days (Bmax = 31 fmol/mg protein, Kd = 1.47 nM), and declined to adult levels by 26 days (Bmax = 17 fmol/mg protein, Kd = 1.39 nM). In contrast, forebrain concentrations of CCK measured by radioimmunoassay rose monotonically through day 27. Possible implications of the transient developmental peak of CCK receptors are discussed.

Cholecystokinin receptors in brain: effects of obesity, drug treatment, and lesions.

High affinity binding sites specific for cholecystokinin (CCK) and related peptides have been identified in brain. These receptors are regionally distributed, with the greatest density in the caudate nucleus and olfactory bulbs. The number of forebrain CCK receptors increases postnatally to a peak density at 12 days of age and then falls to adult concentrations by 26 days of age. Cerebral cortical (but not hypothalamic) CCK receptors were 15-18% higher (p less than 0.05) in obese rats and mice when compared with their lean littermates; however, CCK receptors were unchanged after 96 hours of fasting in normal rats. Chronic reserpine treatment (0.75 mg/kg/day X 7 days) caused a 48% increase (p less than 0.001) in the number of cerebral cortical CCK receptors, but had no effect on receptors in the caudate nucleus. Chronic d-amphetamine sulfate (5 mg/kg twice daily X 7 days) had no effect on CCK binding in cortex or caudate nucleus. Approximately 75% of the CCK receptors in the caudate nucleus are susceptible to destruction by kainic acid, indicating that they are predominantly localized to neuronal cell bodies; the remaining 25% were destroyed by severing caudal afferents to the caudate nucleus, indicating a possible presynaptic localization.

Neuropeptide modulation of social and exploratory behaviors in laboratory rodents.

Neuropeptide influences on exploratory and social behaviors were investigated, using a video-monitored computer-assisted automated animal behavior analysis system. Cholecystokinin decreased exploratory tendencies in the dose range 0.1-5.0 microgram/kg IP and 0.5-5.0 microgram/IVT, indicating a peripheral mechanism in the CCK reduction of spontaneous behaviors. Neither arginine vasopressin nor alpha-melanocyte stimulating hormone changed parameters of exploratory and social behaviors, strengthening the possibility that their roles in increasing acquisition and retention of operant tasks are specific to neural mechanisms involved in memory and learning. Analysis of spontaneous exploratory and social behavior patterns appears to be a sensitive and effective tool for detecting changes in arousal and attention to environmental stimuli which may underlie more specific behavioral effects of brain neuropeptides.

Prolactin releasing potencies of antipsychotic and related nonantipsychotic compounds in female rats: relation to clinical potencies.

Prolactin responses to various intraperitoneal doses of nine antipsychotic and related nonantipsychotic compounds were measured in the sera of female rats. At doses of 50 mg/kg or less, all drugs stimulated prolactin. Dose-response curves indicated the following order of prolactin stimulating potency: haloperidol greater than reduced haloperidol congruent to lenperone greater than chlorpromazine greater than AHR-1900 greater than thioridazine greater than clozapine greater than U-25927 greater than SCH-12679. This ranking does not agree entirely with the ranking of relative antipsychotic potency of these compounds. The butyrophenone AHR-1900 is inactive clinically, whereas clozapine is a more potent antipsychotic agent than chlorpromazine. The relation between prolactin-stimulating potency and reported clinical potency was improved by comparing drugs within the same chemical classification: AHR-1900 was only one-sixtieth as potent as haloperidol in stimulating prolactin secretion. Reduced haloperidol, a major metabolite of haloperidol, was one-fourth as potent as haloperidol in stimulating prolactin release, suggesting that the potential antipsychotic activity of reduced haloperidol should be investigated.

Variability of prolactin response to intravenous and intramuscular haloperidol in normal adult men.

Serum prolactin (PRL) concentrations were monitored in seven normal adult men for 1 h before and 7 h after i.v. and i.m. injection of 0.25 mg and 0.50 mg haloperidol. The magnitude of the PRL response was dose-related but quite variable across subjects. The patterns of PRL secretion over the 7 h post-injection period also varied greatly among the subjects. Differences in serum heloperidol concentrations accounted for 88% of the variability in the magnitude of the PRL response to the 0.5 mg IM haloperidol dose, but only accounted for 60% of the PRL variability following the 0.5 mg IV dose. The pattern of haloperidol disappearance from serum was similar across the seven subjects and thus unrelated to the variable patterns of PRL response.