Biomedical subjects

L Steardo

Publications and source records attributed to L Steardo.

At least 55 records · Page 3Linked to original sources

PubMed1987

Protein kinase C mediates the stimulation by somatostatin of dopamine synthesis in the rat striatum and nucleus accumbens.

In experiments using a synaptosomal preparation from the striatum and nucleus accumbens, somatostatin caused a dose-dependent increase in dopamine synthesis. This increase was additive with that produced by 8-BrcAMP but not with that produced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and was blocked by the protein kinase C inhibitor polymyxin B (PMB). These findings suggest that stimulation of dopamine synthesis by somatostatin is mediated by activation of protein kinase C.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

Brain barrier tissues: end organs for atriopeptins.

Little is known about the pathophysiology of cerebral edema and other disturbances of water balance that involve the barrier tissues at the interface of blood and brain. The present experiments show that these barrier tissues contain receptors and second messenger systems for atriopeptins, recently identified cardiac peptides involved in peripheral water regulation. They also show that atriopeptins can alter the rate of cerebrospinal fluid production. Because the blood-brain and blood-cerebrospinal fluid barriers are involved in normal water movements in the central nervous system, these studies suggest that brain barrier tissues may be important end organs for the atriopeptins and that atriopeptins could have therapeutic application to disorders of water balance in the central nervous system. An isolated, purified population of atriopeptin receptor cells, obtained from choroid epithelium, was used in these experiments. This cell population may provide a valuable model system for investigating the intracellular biochemical mechanisms through which atriopeptins exert their actions.

Adenylyl Cyclases↗

PubMed1987

Gonadal steroids do not affect basal growth hormone response to naloxone in humans.

Evidence has accumulated that endogenous hypothalamic opioid activity fluctuates through the menstrual cycle depending upon the ovarian steroid milieu. In fact, naloxone, the specific opiate antagonist, is more effective in producing neuroendocrine changes in the late follicular and midluteal phases of the menstrual cycle, when the functional activity of hypothalamic opiate system is high. In order to investigate a possible regulatory function of endogenous opioids on basal growth hormone (GH) secretion in humans, we studied the basal GH response to naloxone (2 mg iv as a bolus) in different phases of the menstrual cycle in ten regularly menstruating women and in eight hypogonadal (postmenopausal) females before and after estrogen treatment. This protocol was carried out to test the hypothesis that estrogens could sensitize basal GH response to opiate receptor blockade. The results do not support this view and suggest that, under basal conditions, hypothalamic opiates have minimal influence on GH secretion in humans.

Adult↗

PubMed1987

Impaired growth hormone response to sodium valproate in normal aging.

Evidence has been provided for impaired neurotransmitter functioning in the brain of elderly subjects. In order to assess central GABAergic transmission, the activity of the hypothalamic GABA system may be investigated by basal growth hormone (GH) response to the GABAergic drug sodium valproate (SV). For this purpose 15 healthy men (aged 19-81 years) received orally 800 mg SV or placebo tablets on two different occasions, 1 week apart. Blood samples were collected before and after drug administration for determining GH and SV plasma levels. A clear-cut increase in plasma GH was observed following SV (P less than 0.001 in young persons, P less than 0.005 in old subjects), but in the aged subjects this rise was statistically lower than in the young men (P less than 0.001 at t = 90 min). No difference was observed in basal GH levels and in SV plasma concentrations between elderly and young subjects. delta GH (= maximum post-SV GH level minus baseline GH value) was significantly inversely related to age (r = -0.90, P less than 0.001). These results may suggest an impaired hypothalamic-pituitary responsiveness to a pharmacological challenge enhancing endogenous GABA tone in the elderly.

Adult↗

PubMed1987

Cholecystokinin stimulates dopamine synthesis in synaptosomes by a cyclic AMP-dependent mechanism.

The effects of different fragments of cholecystokinin (CCK) on dopamine synthesis were studied in synaptosomal preparations from the striatum, substantia nigra, and frontal cortex. In striatal synaptosomes, dopamine synthesis rate measured by dopamine accumulation was 12.5% lower than that measured by 3,4-dihydroxyphenylalanine (DOPA) accumulation; however, K+-accelerated synthesis was the same for both methods. Synthesis rate was independent of exogenous tyrosine levels. In the three regions studied, the combined stimulatory effects of 8-Br-cyclic AMP and high K+ were additive. CCK-5, CCK-3, CCK-27-33, and CCK-8 (sulphated) enhanced synthesis, CCK-5 being the most potent fragment. The nonsulphated octapeptide had no effect. In all three regions, CCK-5 and high K+ had an additive effect on dopamine synthesis; CCK-5 and 8-Br-cyclic AMP together produced the same enhancement of synthesis as CCK-5 alone. CCK-5 produced similar dose-dependent increases in dopamine synthesis and cyclic AMP accumulation in striatal synaptosomes, and both effects were blocked by the CCK antagonist proglumide.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1987

Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression?

The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs.

Adult↗

PubMed1986

Pharmacological evidence for a dual GABAergic regulation of growth hormone release in humans.

Effects of sodium valproate, which is believed to act via a gamma-aminobutyric acid mechanism, on basal and exercise-induced rise of growth hormone release have been tested in eighteen healthy volunteers. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. 600 mg per os of the drug resulted in a significant enhancement in plasma hormonal concentrations, whereas no effects were induced by placebo (p less than 0.005). Conversely, the growth hormone rise stimulated by exercise was markedly inhibited by sodium valproate (p less than 0.001 and p less than 0.01 at time 20, 40 and 60 min respectively). The results of this study are consistent with the hypothesis that a dual GABAergic control of growth hormone secretion is present in man.

Adult↗

PubMed1986

Vasopressin release after enhanced serotonergic transmission is not due to activation of the peripheral renin-angiotensin system.

Pharmacological enhancement of 5-hydroxytryptamine (5-HT) transmission increases plasma vasopressin in rats. To investigate whether this effect is mediated through activation of the peripheral renin-angiotensin system, plasma vasopressin concentrations were measured after 5-HT activation in rats with lesions of the subfornical organ or pretreated with saralasin. The results show that the 5-HT-induced elevation of vasopressin is not due to activation of the peripheral renin-angiotensin system.

Animals↗

PubMed1986

The effect of bromocriptine on plasma catecholamine concentrations in normal volunteers.

The effect of the ergot derivative bromocriptine (5 mg orally) on blood pressure and plasma catecholamine concentrations was explored in normal volunteers. A significant decrease of plasma noradrenaline was found, while dopamine and adrenaline concentrations did not change significantly. Systolic and diastolic blood pressures were significantly lowered at 150 min after administration. The hypotensive effect of bromocriptine seems to be mediated by a lowered release of noradrenaline from sympathetic nerve endings. It may be hypothesized that the drug stimulates presynaptic dopamine receptors located on postganglionic sympathetic nerves, thus inhibiting noradrenaline discharge.

Adult↗

PubMed1986

Growth hormone response to sodium valproate in chronic schizophrenia.

The hypothesis of a gamma-aminobutyric acid (GABA) involvement in the pathophysiology of schizophrenia has been recently proposed but not confirmed. As GABA has been shown to affect basal growth hormone (GH) secretion in humans, the assessment of plasma GH response to a GABAergic drug, such as sodium valproate (SV), in schizophrenic subjects might be a tool with which to investigate central GABA activity in this illness. For this purpose, we administered orally 800 mg of SV or placebo to 13 chronic schizophrenics and to 10 normal controls, and measured plasma GH levels before and after the drug administration. SV enhanced basal GH secretion in healthy male volunteers, but not in chronic schizophrenics. These results suggest a defect of the endogenous GABA system in chronic schizophrenia. Whether the reduced responsiveness observed represents a primary defect or a secondary alteration of the GABA system in schizophrenia is as yet unknown.

Adult↗

PubMed1986

Carbamazepine lowering effect on CSF somatostatin-like immunoreactivity in temporal lobe epileptics.

The effect of carbamazepine treatment on CSF-somatostatin-like immunoreactivity (SLI) in patients suffering from temporal lobe epilepsy was investigated. A baseline lumbar puncture was performed on 12 patients and 10 normal volunteers. A second tap was repeated only in patients when they were on peak of carbamazepine concentration for 10 days. Levels of CSF-SLI were measured by RIA. No significant differences were found in CSF-SLI basal concentrations between epileptics and controls, whereas a significant decrease (p less than .0002 Duncan's multiple range test) of CSF peptide levels occurred in 9 of 12 patients under medication. Although the neural mechanism through which carbamazepine lowers CSF-SLI is still unknown, the results of the present study suggest that the reported effect might be part of the apparatus by which carbamazepine exerts its anticonvulsant action.

Adolescent↗

PubMed1986

Huntington's disease: effect of cysteamine, a somatostatin-depleting agent.

Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels.

Adult↗

PubMed1985

Effect of substances influencing brain serotonergic transmission on plasma vasopressin levels in the rat.

Studies were carried out in the rat to investigate whether serotonin (5-HT) is involved in the regulation of vasopressin (ADH) release. For this purpose plasma ADH levels were measured in rats treated with drugs enhancing 5-HT transmission, such as d-fenfluramine and quipazine and with 5-HT depleting drugs, p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT). Forebrain 5HT, noradrenaline (NA) and dopamine (DA) were also measured. d-Fenfluramine and quipazine induced dose-related increases in plasma ADH levels in normohydrated rats. The effects of quipazine and d-fenfluramine were prevented by PCPA, indicating that 5-HT transmission was required for the biologic response. 5,7-DHT and PCPA pretreatment decreased forebrain 5-HT content and prevented ADH increases involved by water deprivation, suggesting that 5HT is necessary for the hormonal response to osmotic stimuli. The results summarized imply that serotonin may have a role in the physiological release of ADH from neurohypophysis.

5,7-Dihydroxytryptamine↗

PubMed1985

Products of cholecystokinin (CCK)-octapeptide proteolysis interact with central CCK receptors.

Peptidases present in central nervous system (CNS) synaptic membranes, hydrolyze the neuroactive peptide cholecystokinin-octapeptide (CCK-8; Asp-Tyr-SO3H-Met-Gly-Trp-Met-Asp-Phe-NH2). In order to determine the pathway of degradation, synthetic CCK-8 was incubated at 37 degrees C with purified synaptic membranes; at various intervals reaction samples were removed from the reaction mixture and analysed by high-performance liquid chromatography to identify and quantify the peptide fragments. The results indicate an initial endopeptidase cleavage at the Met-Gly bond producing CCK-5 (Gly-Trp-Met-Asp-Phe-NH2). The carboxyl-terminal pentapeptide is further proteolysed to CCK-4 (Trp-Met-Asp-Phe-NH2) by a puromycin-sensitive aminopeptidase and to CCK-3 (Met-Asp-Phe-NH2) and Gly-Trp by an endopeptidase action. CCK-3 and CCK-2 appear to be relatively stable end-products. Moreover, these proteolytic fragments are shown to bind to the CCK receptor in brain with varying potencies.

Animals↗

PubMed1985

Evidence for a GABAergic control of the exercise-induced rise in GH in man.

The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABAergic regulation of GH secretion in man, at least under certain physiological conditions.

Adult↗

PubMed1985

Effect of nicotine on drinking and diuresis in septal lesioned rats.

Lesions of septal nuclei in rats enhance water intake and urine outflow. The effects of nicotine tartrate (2.5 mg/kg) on drinking and diuresis were investigated in normal, sham and septal lesioned rats. Nicotine administration resulted in a surprising hyperdipsia and polyuria in lesioned animals, the mean output rose from 38 +/- 1.3 ml (before treatment) to 101.6 +/- 6.1 (during treatment) and water intake increased from 74.2 +/- 1.8 ml to 129.8 +/- 6.4 ml.

Acetylcholine↗

PubMed1985

Clonidine reverses methylxanthine-induced potentiation of baclofen antinociception.

The effect of clonidine on the antinociceptive effect of methylxanthine/baclofen and dopamine antagonist/baclofen combinations was examined to determine if alterations in noradrenaline turnover might mediate the potentiating effect of these agents. Clonidine alone had intrinsic activity in the tail flick test, so a dose and treatment schedule which produced a plateau effect was chosen. Clonidine pretreatment did not significantly alter the effect of baclofen alone, but reversed the potentiation of the action of baclofen produced by both theophylline and isobutylmethylxanthine. The intrinsic effect of isobutylmethylxanthine also was reversed. Combinations of dopamine antagonists and baclofen were potentiated or unaffected by clonidine. A possible interpretation of these results is that mutual interactions by baclofen and methylxanthines with descending noradrenergic pathways mediate the methylxanthine-induced potentiation of the antinociceptive effect of baclofen. A more specific determination of noradrenergic pathways involved in the action of baclofen will require the use of more specific alternative approaches.

1-Methyl-3-isobutylxanthine↗

PubMed1985

Thirst and vasopressin secretion following central administration of angiotensin II in rats with lesions of the septal area and subfornical organ.

Various dipsogenic stimuli, including peripheral and central administration of angiotensin II, have been shown to be capable of releasing vasopressin from the neurohypophyseal system. Studies were carried out in the rat to investigate whether the septal area, which contains a high concentration of angiotensin-sensitive cells and has neural connections with hypothalamic vasopressin-secreting neurons, mediated the stimulatory effect produced by angiotensin II on vasopressin release. Rats with electrolytic lesions in the region of the septal area had increased daily water consumption and urine output when these lesions included the medioventral or lateral nuclei of the septal forebrain, but not when the lesion involved the subfornical organ. No difference was observed in drinking responses following water deprivation or intracerebroventricular injection of angiotensin II in all experimental groups. In addition, the impaired ability to maintain water homeostasis (polyuro-polydipsic syndrome) of septal-lesioned rats was associated septal-lesioned rats was associated with decreased levels of circulating radioimmunoassayable vasopressin. Furthermore, the vasopressin release which occurred in response to intracerebroventricular angiotensin II in normal controls, sham-lesioned and subfornical organ-lesioned rats was significantly attenuated in rats with electrolytic lesion of the medioventral or lateral septal area. Since cells in the lateral septal area are excited by iontophoretic application of angiotensin II, the present data might be consistent with the hypothesis that the stimulatory effect produced by central administration of angiotensin II on vasopressin release rests upon the integrity of the lateral septal area.

Angiotensin II↗