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Biomedical subjects

L Steardo

Publications and source records attributed to L Steardo.

At least 37 records · Page 2Linked to original sources
PubMed1994

Selective activation of glutamate receptor NMDA subtype induces plasma vasopressin increase in rats.

Studies were carried out in the rat to investigate whether glutamic acid is involved in the regulation of vasopressin (VP) release. For this purpose plasma VP levels were measured in rats treated with the glutamate agonist N-methyl-D-aspartate (NMDA). In our experimental conditions NMDA induced dose-related increases in plasma VP levels in normohydrated rats. The effect of NMDA were prevented by 3[(+)-2 carboxy-piperazine-4-yl]propyl-1-phosphonic acid (CPP), a selective and competitive antagonist of NMDA receptors. These data show that glutamate may contribute to the physiological release of VP from the neurohypophysis.

Animals↗
PubMed1993

Heterologous sensitization of adenylate cyclase activity by serotonin in the rat cerebral cortex.

In vitro exposure of rat cerebrocortical slices to microM concentrations of serotonin (5HT) results in an increased response of adenylate cyclase to isoproterenol (ISO). No change in the affinity of the beta-adrenoceptor toward the agonist was found after 5HT exposure when measuring ISO displacement of [3H]CGP 12177 binding. A similar increase of adenylate cyclase response was also found when using VIP as a stimulatory agent. The dose-response curve of adenylate cyclase to the GTP analogue, GppNHp, was modified by 5HT, which promotes a significantly higher maximal response without altering the potency of GppNHp. Forskolin-stimulated adenylate cyclase activity was not affected by 5HT. Serotonergic 5HT2 receptors are involved in the sensitization of adenylate cyclase to GppNHp, since the selective 5HT2 antagonist ketanserin inhibits the effect of 5HT, whereas the 5HT2 agonist DOI mimics 5HT. The involvement of 5HT2 receptor-coupled activation of protein kinase C is also demonstrated: direct protein kinase C activators such as phorbol esters and s,n-dioctanoylglycerol behave in the same manner as 5HT, while the protein kinase C inhibitor CGP 41251 prevents 5HT from increasing adenylate cyclase responsiveness to GppNHp. Moreover, in vitro exposure of cortical slices to 5HT results in reduced inhibition of adenylate cyclase by somatostatin. Since no change was observed at the receptor level and in the direct stimulation of the catalytic subunit of the enzyme, we propose that 5HT might accomplish the sensitization of adenylate cyclase through protein kinase C by inactivating the inhibitory coupling protein Gi and facilitating the interaction of the exogenous GppNHp with the stimulatory coupling protein Gs.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Impaired sensitivity of the hypothalamo-pituitary-thyroid axis to the suppressant effect of dexamethasone in elderly subjects.

It has been shown that glucocorticoids have a suppressant effect on the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in young men. To assess whether this effect of corticosteroids is also present in aged individuals, six young subjects (aged 26-32 years) and six elderly men (aged 68-75 years) underwent, in random order, at 1 week intervals, three TRH stimulation tests 30 min after IV administration of placebo and 2 mg and 4 mg dexamethasone phosphate. Elderly men showed higher basal plasma levels of TSH (P less than 0.02) and lower plasma levels of FT3 (P less than 0.03) and FT4 (P less than 0.01). The TSH response to TRH was significantly lower in aged subjects than in young ones (P less than 0.009). Moreover, 2 mg dexamethasone significantly blunted the TSH response to TRH in young men (P less than 0.0001), but not in the elders. The inhibitory effect of the glucocorticoid on the TRH-induced TSH secretion, in aged subjects, was evident only after 4 mg dexamethasone administration (P less than 0.0001). These data confirm that glucocorticoids have an inhibitory role on the thyrotropic axis and show, for the first time, that normal elderly men are hyporesponsive to this suppressant effect of corticosteroids.

Adult↗
PubMed1991

Failure of single electroconvulsive shock to affect daytime melatonin production in rats.

It has been reported that, in the rat, different types of stressful procedures increase daytime melatonin production. Electroconvulsive shock (ECS) has been shown not to affect daytime pineal melatonin in rats killed 9 hr after its administration. It is possible that the long-lasting interval between the ECS administration and the sacrifice of the animals obscured an effect of the stressful procedure. In the present study, the effects of acute ECS on daytime melatonin production were evaluated in both ECS- and sham-treated rats killed 30, 60, 120, and 240 min after treatment. As compared with the sham-treated animals, rats receiving acute ECS (80 mA, 0.5 sec) did not show any significant difference in either pineal or serum melatonin levels at any time point after treatment. These data indicate that single ECS does not affect daytime melatonin production in the rat and suggest that the pineal gland may respond differently to the various stressful procedures.

Analysis of Variance↗
PubMed1990

Chronic antidepressant drug treatment does not affect GH response to baclofen in depressed subjects.

The growth hormone (GH) response to baclofen, a specific GABAB agonist, was tested in 8 male depressed patients before and after chronic treatment with amitriptyline (100 mg/day). No difference was seen in plasma GH response before and 28 days after amitriptyline treatment, suggesting that chronic antidepressant drug treatment does not increase hypothalamic GABAB receptor sites in humans. These data suggest that further studies need to support the hypothesis of a GABA involvement in the mechanism of action of antidepressant drugs.

Adult↗
PubMed1990

Evidence that cholinergic receptors of muscarinic type may modulate vasopressin release induced by metoclopramide.

Studies were carried out in the rat in order to investigate whether cholinergic mechanisms may be involved in vasopressin (VP) release induced by metoclopramide (MCP). The intravenous injection of MCP induced dose-related increases in plasma VP levels in water-loaded rats. These effects were prevented by atropine sulphate, but not by pirenzepine hydrochloride indicating that activation of cholinergic receptors of M-2 type was possibly required for the biologic response.

Animals↗
PubMed1990

Alpha 2-adrenergic stimulation within the nucleus tractus solitarius attenuates vasopressin release induced by depletion of cardiovascular volume.

The functional role of the nucleus tractus solitarius (NTS) in the regulation of arginine-vasopressin (AVP) release mediated by baroreceptor activation was investigated by examining the effects induced by the presynaptic alpha-adrenergic agonist clonidine. The present data show that microinjection of clonidine into NTS resulted in a significant attenuation of AVP secretion induced by hypovolemia in the rat. This effect produced by NTS injection of 8 and 10 nmol clonidine was prevented by NTS pretreatment with the alpha 2-adrenoceptor blocker, yohimbine (10 nmol), indicating alpha 2-adrenergic receptors were required for the biological response. These findings suggest that catecholaminergic projections from NTS to hypothalamic vasopressinergic neurons play a facilitatory role in controlling AVP secretion.

Adrenergic alpha-Agonists↗
PubMed1990

GABA, depression and the mechanism of action of antidepressant drugs: a neuroendocrine approach.

Recent evidence has suggested the involvement of the GABAergic system in depression and in the mechanism of action of somatic antidepressant treatments. In particular, GABAB receptors have been found to be increased in the rat frontal cortex following chronic antidepressant therapies. In the present study, the sensitivity of GABAB binding sites was assessed in nine healthy men and 10 depressed patients via the plasma growth hormone (GH) response to acute baclofen administration (20 mg p.o.). Depressed subjects were tested before and after 15 and 35 days of treatment with amitriptyline (100 mg/day), imipramine (100 mg/day) and fluoxetine (20 mg/day). GH response to acute GABAB receptor activation did not differ between depressed subjects and healthy controls. Moreover, chronic antidepressant treatment did not significantly modify this response, even when a clear therapeutic effect was obtained. These results do not support the idea that GABAergic mechanisms are involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs.

Adult↗
PubMed1989

Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging.

The plasma GH response to human pituitary GH (hpGH)-releasing hormone-40 (hpGHRH-40; 1 microgram/kg BW) was significantly lower in seven healthy aged men (age range, 65-78 yr) than in seven healthy young men (age range, 18-31 yr) 30, 60, and 90 min after acute hpGHRH-40 administration (P less than 0.0001, by Student's unpaired t test). To verify whether a priming regimen might be able to reverse the reduced GH response to GHRH, elderly subjects underwent repetitive administration of hpGHRH-40 and placebo in a double blind design (100 micrograms hpGHRH-40 or volume-matched saline iv as a single morning dose, every 2 days for 12 days). After the hpGHRH-40-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points after placebo treatment. These findings suggest that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response.

Adult↗
PubMed1988

Neuroanatomical and biochemical evidence for the involvement of the area postrema in the regulation of vasopressin release in rats.

Studies were carried out in the rat to determine if the area postrema (AP), a medullary circumventricular organ, might be involved in the control of vasopressin (VP) release. The data from this study demonstrate the existence of direct neural connections between the AP and the hypothalamic VPergic neurons of the supraoptic nucleus (SON) as showed by the retrograde tracer horseradish peroxidase (HRP). Labeled neurons were observed in the AP following HRP injections into the SON. In addition, rats with AP lesions showed an impaired ability to conserve water and concentrate their urine in response to an hypertonic NaCl load. They, also, failed to maintain sodium retention and showed an attenuation of VP release during intracellular dehydration. These findings indicate that AP plays an important role in the regulation of VP release during changes in osmotic environment and suggest that this medullary circumventricular organ is a part of central circuitry subserving salt-water balance.

Animals↗
PubMed1988

Prolactin response to sodium valproate in schizophrenics with and without tardive dyskinesia.

Sodium valproate, a GABAergic agent (800 mg), and placebo were administered orally, as a single dose, to nine chronic schizophrenics with tardive dyskinesia (TD), seven chronic schizophrenics without TD and ten healthy controls, according to a double blind design. Blood samples were collected before and after drug administration, to determine plasma prolactin concentrations. Sodium valproate decreased plasma prolactin levels in healthy subjects (P less than 0.001) and in schizophrenic patients with TD (P less than 0.001), but not in chronic schizophrenics without TD. Moreover, in dyskinetic subjects, the maximum per cent decrease of plasma prolactin from basal value was positively correlated to the score of the abnormal involuntary movement scale (r = 0.724, P less than 0.02). Although the neural or biochemical substrate underlying the different responses of plasma prolactin to sodium valproate in schizophrenics with and without TD remains unclear, these results provide the first neuroendocrine evidence able to differentiate dyskinetic subjects from those without TD within a schizophrenic population.

Adult↗
PubMed1988

Baclofen-induced growth hormone secretion is blunted in chronic schizophrenics: neuroendocrine evidence for a GABA disturbance in schizophrenia.

To substantiate a previously reported disturbance of gamma-aminobutyric acid (GABA) in chronic schizophrenia, plasma growth hormone (GH) response to a direct GABA agonist (baclofen, 10 mg) was assessed in 12 unmedicated chronic schizophrenic males and 10 sex- and age-matched healthy controls. Baclofen and placebo were administered orally, in a double-blind design, and blood samples were collected before and 30, 60, 90, 120, 180, and 240 min after drug or placebo administration. Baclofen induced a clear-cut rise in plasma GH levels over baseline values, but the GH increase observed in the patients was significantly smaller than that in controls. These results support the idea that GABA mechanisms may be impaired in chronic schizophrenia.

Adult↗
PubMed1988

Selective damage of neuron perikarya in the medial septum of the rat forebrain: effects on food and water intake, urine output and body weight.

The intraseptal administration of the neurotoxin kainic acid (KA) induced a significant depletion of the neuronal population and glial proliferation in medial septal areas. The behavioral effects induced by this selective destruction of the neurons indigenous to the medial septal areas were investigated. KA produced a marked increase in urine output and a transient reduction in body weight, but failed to affect water and food intake.

Animals↗
PubMed1988

Pharmacological activation of the GABAergic system does not affect GH and PRL release in acromegaly.

An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.

Acromegaly↗
PubMed1988

Combined alpha-adrenergic stimulation results in biphasic response of growth hormone release in man.

Oral clonidine administration or insulin-induced hypoglycemia may enhance GH secretion through alpha 2-adrenergic stimulation in man. To further characterize the role of adrenergic transmission in the regulation of GH release, the effects of combined administration of clonidine and insulin were investigated in 16 normal men randomly assigned to 2 groups. The first group received 0.1 U/kg regular insulin, iv, followed by placebo or clonidine (0.150 mg), orally, on 2 different days, 2 weeks apart. The second group received oral clonidine (0.150 mg), followed by iv placebo or insulin (0.1 U/kg) on 2 different days, 2 weeks apart. Insulin induced a clear-cut increase in plasma GH (F = 79.88; P less than 0.001) that was not affected by placebo, whereas it was significantly inhibited by oral clonidine (P less than 0.001 at 60, 90, and 120 min). Similarly, oral clonidine administration resulted in a clear-cut rise in plasma GH levels (F = 16.44; P less than 0.001) that was significantly reduced by insulin (P less than 0.001, P less than 0.02, and P less than 0.05 at 60, 90, and 120 min, respectively). These results suggest that while moderate activation of the alpha 2-adrenergic system stimulates GH release, further stimulation of the same system may result in inhibition, rather than further activation, of GH secretion.

Adult↗
PubMed1988

Evidence for a sex difference in the basal growth hormone response to GABAergic stimulation in humans.

Evidence has been provided supporting the existence of a sex-related difference in the GH secretion following different GH-releasing stimuli. Since pharmacological activation of the endogenous gammaaminobutyric acid (GABA) system results in increased basal GH release in humans, the present study was undertaken to investigate whether a sex difference is present in the GH response to GABAergic stimulation. Sixteen healthy subjects (8 women and 8 men) received orally 10 mg of baclofen, the direct GABAB agonist which freely crosses the blood-brain barrier. Blood samples were collected before (T = -30 and 0) and 30, 60, 90, 120 and 180 min after the drug administration for plasma GH measurements. Following baclofen administration, plasma GH rose in healthy males (F = 19.417, P less than 0.0001), but not in females (F = 1.67, NS). These results suggest that GABA modulation of human GH release is sex-dependent.

Adult↗