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Biomedical subjects

G Schettini

Publications and source records attributed to G Schettini.

At least 109 records · Page 6Linked to original sources
PubMed1991

Role of interleukin-6 in the neuroendocrine system.

Interleukin-6 (IL-6) is a pleiotropic cytokine exerting many immunological and non immunological actions. The cytokine binds to a specific receptor, whose activation induces the association with a novel transducer, the glycoprotein gp 130. Here we present our results about the effect of IL-6 on both hormone secretion and second messenger systems at pituitary level, and the production of IL-6 from cells of central nervous system. IL-6 inhibited basal, VIP and TRH-stimulated prolactin (PRL) secretion from single lactotropes, studied by means of reverse hemolytic plaque assay, whereas in primary cultures of anterior pituitary cells, according to the literature, the cytokine stimulated prolactin secretion. IL-6 did not affect basal adenylate cyclase activity, inositol phosphate production, and cytosolic calcium concentration. Conversely, the preincubation of pituitary cells with interleukin-6 for 20 min significantly reduced VIP- and forskolin-stimulated adenylate cyclase activity, as well as inositol phosphate production and free cytosolic calcium increase induced by TRH.

Adrenocorticotropic Hormone↗
PubMed1990

[The cardiac toxicity of antidepressive thymoleptics. Experimental and clinical studies].

The aim of the present review was: 1) to analyse the effects of tricyclic antidepressant compounds on the conduction system of the heart, the heart rate, the left ventricular function and the blood pressure; 2) to describe the methods used in order to evaluate these parameters both in vitro and in vivo; 3) to summarize all the data available on cardiovascular side effects of the newer antidepressants.

Animals↗
PubMed1990

[ACE-inhibitors: physiologic premises and pharmacologic profiles].

In the present paper the authors review the results of more than ten years' experience with ACE-inhibitors in the therapy of hypertension and congestive heart failure. The importance of tissue rather than serum ACE level for the long-term response to these agents has been mainly stressed. Clinical studies have shown the importance of these agents for the general practitioner in view of both their efficacy and the low incidence of untoward effects. If further studies succeed in showing the extent to which individual mechanisms of action of ACE inhibitors contribute to the overall therapeutic effect it can be expected that it will become possible to synthetize new molecules with more selective action. Considering the hypothesis according to which these agents are also effective for the prevention and management of myocardial infarction and in the management of chronic renal failure, these studies would appear to be particularly urgent.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Rapid and long-lasting suppression of prolactin secretion and shrinkage of prolactinomas after injection of long-acting repeatable form of bromocriptine (Parlodel LAR).

Five patients with PRL-secreting macroadenoma and nine patients with PRL-secreting microadenoma or idiopathic hyperprolactinaemia were treated with monthly administrations of long-acting bromocriptine suitable for repeatable injections (Parlodel LAR) for 1-12 cycles of treatment. A significant shrinkage of tumour mass and the recovery of visual field defects were observed in patients with macroprolactinoma. Plasma PRL levels decreased to 16.8 and 18.1% of pretreatment values, in macroprolactinoma and idiopathic or microadenomatous hyperprolactinaemic subjects, respectively, during the first cycle of treatment, reaching the normal range in three patients of each group. During the following cycles of treatment, two patients with macroprolactinoma and one patient with idiopathic or microadenomatous hyperprolactinaemia became normoprolactinaemic. Adverse reactions generally did not last beyond the first days of administration and decreased with the progression of the treatment. In conclusion, its effectiveness and the fact that it is well tolerated, may suggest that this form of bromocriptine may be used as a first therapeutic approach for patients with PRL-secreting adenomas, particularly when shrinkage of a macroadenoma is urgently required.

Adolescent↗
PubMed1990

Modulation of dihydropyridine-sensitive calcium channels: a role for G proteins.

The present study investigates the effect of G protein activation on dihydropyridine recognition sites in PC12 cell membranes. The addition of a stable analogue of GTP, GMP-PNP, increases the displacement of tritiated PN 200-110 produced by Bay K 8644 without modifying the one produced by nitrendipine. This effect is prevented by Pertussis toxin treatment. Functional studies based on the measurement of intracellular calcium concentrations by means of the fura 2 technique show that Pertussis toxin reduces the ability of Bay K8644 to potentiate the increase of cytosolic calcium elicited by 80 mM K+. The results support the hypothesis that a G protein may modulate the activity of voltage-dependent, dihydropyridine-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Interleukin-1-beta modulation of prolactin secretion from rat anterior pituitary cells: involvement of adenylate cyclase activity and calcium mobilization.

Recent findings indicate that interleukin-1 beta (IL1 beta), a monokine secreted by stimulated macrophages and monocytes, modulates neuroendocrine functions in a manner similar to classical hormones. In this study we show that IL1 modulates PRL secretion, assessed by reverse hemolytic plaque assay, and describe the effect of the monokine on adenylate cyclase activity and calcium fluxes in rat normal pituitary cells. In basal and vasoactive intestinal peptide (VIP)-stimulated conditions, low doses of IL1 reduced the mean plaque area, a direct index of PRL secretion without affecting the percentage of PRL-secreting cells. Similarly, low concentrations of IL1 inhibited adenylate cyclase activity in both basal and VIP-stimulated conditions, while higher concentrations restored the enzymatic activity to the control value. IL1 also caused a biphasic effect on the free intracellular calcium increase induced by maitotoxin, a calcium channel activator, being inhibitory at low and stimulatory at high concentrations. The effects of IL1 on adenylate cyclase activity and calcium fluxes were reversed by preincubation of the monokine with its polyclonal antibody, thus confirming the specificity of the effects. In conclusion, our data show that IL1 modulates PRL secretion by acting directly on pituitary cells through interaction with the adenylate cyclase-cAMP system and calcium flux.

Adenylyl Cyclases↗
PubMed1990

Adenosine and its analogue (-)-N6-R-phenyl-isopropyladenosine modulate anterior pituitary adenylate cyclase activity and prolactin secretion in the rat.

The effect of adenosine and its analogue (-)-N6-R-phenylisopropyladenosine (PIA) on both anterior pituitary adenylate cyclase activity and prolactin secretion was examined in the rat. Adenosine inhibited basal adenylate cyclase activity in a dose-dependent manner and also reduced the stimulation of the enzyme by vasoactive intestinal peptide (VIP). Likewise, in primary cultures of anterior pituitary cells, adenosine decreased prolactin secretion in both basal and VIP-stimulated conditions. In perifusion experiments, adenosine also inhibited prolactin release in both basal and TRH-stimulated conditions. PIA produced a biphasic pattern of response of basal adenylate cyclase activity, being inhibitory at low and stimulatory at high concentrations. In VIP-stimulated conditions, low concentrations of PIA inhibited both adenylate cyclase activity and prolactin release from primary cultures of pituitary cells, while no additive stimulatory effect was seen at high concentrations. Similarly, low concentrations of PIA reduced both basal and TRH-stimulated prolactin release from perifused pituitaries, while increasing PIA concentrations restored prolactin release. These data show that adenosine affects basal and stimulated prolactin secretion from anterior pituitary cells. Adenosine receptors seem to be coupled to the adenylate cyclase system in the anterior pituitary gland, suggesting a possible relationship between the effect of adenosine on adenylate cyclase activity and prolactin secretion.

Adenosine↗
PubMed1989

Interleukin 1 beta inhibition of TRH-stimulated prolactin secretion and phosphoinositides metabolism.

The effect of interleukin 1 beta on prolactin secretion and on phosphoinositide turnover in anterior pituitary cells was evaluated. Interleukin 1 beta significantly inhibited TRH-stimulated prolactin secretion assessed by the reverse hemolytic plaque assay. In particular, the cytokine reduced the percentage of plaque forming cells, the plaque mean area, the large plaques percentage. TRH-stimulated inositol phosphate production was also significantly inhibited by interleukin 1 beta. This study shows that interleukin 1 beta reduces TRH-induced prolactin secretion through a direct action on pituitary cell, and attenuates the TRH-stimulated phosphoinositide breakdown. This latter effect may suggest that the reduced lactotropes sensitivity to TRH action may be partially due to interleukin 1 beta inhibition of phosphatidylinositol breakdown.

Animals↗
PubMed1989

Somatostatin inhibition of adenylate cyclase activity in different brain areas.

Somatostatin receptors have been identified in different brain areas but the characterization of their postreceptor effect is still lacking. In this study we analyze the somatostatin effect on adenylate cyclase activity in different brain regions, namely frontal cortex, striatum, hypothalamus and hippocampus. Somatostatin inhibited basal adenylate cyclase activity in all brain areas, being maximally effective in the frontal cortex (-42%). Moreover, somatostatin inhibited both dopamine- and norepinephrine-stimulated adenylate cyclase activity in the examined cerebral regions showing a higher effectiveness than in basal conditions. VIP stimulation of adenylate cyclase was also reduced by somatostatin. The peptide inhibited by 50% forskolin-stimulated (10 nM to 10 microM) enzyme activity in frontal cortex and hypothalamus (in hippocampus the inhibition reached only -25%) showing a non-competitive pattern of inhibition. Finally, pertussis toxin pretreatment abolished the somatostatin inhibition of forskolin-stimulated frontal cortex adenylate cyclase activity. These results show that brain somatostatin receptors are coupled in an inhibitory way with adenylate cyclase enzyme that may represent one of the postreceptor mechanisms mediating the somatostatin modulation of brain functions.

Adenylyl Cyclases↗
PubMed1989

[Antiemetic effect of the levo isomer of sulpiride (L-sulpiride) in humans].

Vomiting represents one of the most dangerous complications of general anesthesia. L-sulpiride has been able to control this complication very effectively. We studied the effect on vomiting of two doses of L-sulpiride (50/100 mg). Both these doses have been effective in reducing the episodes of vomiting other than in preventing nausea and retching if considered versus controls and also versus droperidol at the doses of 5 mg (50 mg L-sul = 12%, 100 mg = 4%, droperidol = 20%, controls = 28%). L-sulpiride is an antagonist of dopamine on D2 receptors therefore inhibits the action of dopamine increasing the secretion of prolactin. During the surgical distress per se prolactin levels are increased. Together with the increment of catecholamines, high concentration of prolactin can evoke arrhythmias. In view of this possibility we studied the time course of the administration of the two doses of L-sulpiride and of droperidol on prolactin secretion. Both of the drugs increased the plasma levels of prolactin. Droperidol-induced increase in prolactin secretion was significant already at ten minutes after the administration reaching the peak after 20 minutes. L-sulpiride increased prolactin secretion reaching the maximum increase 20 minutes after the administration of 50 mg of the drug, and 30 minutes after the administration of 100 mg doses. The hyperprolactinemizing action of droperidol lasts for at least 8 hours, whereas L-sulpiride action lasts 4 hours.

Adolescent↗
PubMed1988

Effect of interleukin 1 beta on transducing mechanisms in 235-1 clonal pituitary cells. Part I: Modulation of adenylate cyclase activity.

In the present study we evaluated the effect of interleukin 1-beta on adenylate cyclase activity in 235-1 pituitary cell line. The dose-response curve of interleukin 1 beta effect on adenylate cyclase activity showed a significant inhibition of basal enzyme activity at 1 pM concentration, while the inhibition of forskolin stimulated adenylate cyclase activity was more pronounced and evident at both 0.01 and 1 pM concentrations. The action of the monokine on basal enzyme activity was almost completely reverted by polyclonal anti interleukin 1 beta antibody. The incubation of the cells for 48h with interleukin 1 beta showed a different pattern of response. The inhibitory effect of interleukin 1 beta on adenylate cyclase activity disappeared, while the highest concentration of interleukin 1 beta tested, caused a meaningful stimulation of adenylate cyclase activity which is not present in acute condition. These data show that interleukin 1-beta interacts with the cAMP-generating system in the 235-1 clonal pituitary cells.

Adenylyl Cyclases↗
PubMed1988

Effect of interleukin 1 beta on transducing mechanisms in 235-1 clonal pituitary cells. Part II: Modulation of calcium fluxes.

In the present study we investigated the effect of the interleukin 1 beta on intracellular free calcium concentrations in 235-1 cell line both in basal conditions and after stimulation by the calcium channel activator maitotoxin. Interleukin 1 beta (from 0.01 pM to 10 nM) was unable to significantly affect basal cytosolic free calcium levels in acute conditions. The preincubation of these cells with interleukin 1 beta for 48h modulates maitotoxin stimulation of calcium fluxes without modifying basal intracellular free calcium levels. Low concentrations of interleukin 1 beta (0.01 pM, 1 pM) caused a marked reduction of intracellular free calcium concentrations increase induced by maitotoxin while higher doses of the monokine potentiated maitotoxin stimulation of calcium fluxes. The specificity of interleukin 1 beta effect was tested by means of polyclonal anti-interleukin 1 beta antibody (titer 1:100) which significantly abolished the inhibitory effect of interleukin 1 beta on free cytosolic calcium levels. These results show that a long lasting interaction of interleukin 1 beta with its receptor is able to influence voltage-sensitive calcium channels activation induced by maitotoxin in 235-1 cells.

Animals↗
PubMed1988

Somatostatin and SMS 201-995 reverse the impairment of cognitive functions induced by cysteamine depletion of brain somatostatin.

The involvement of somatostatin in the organization of cognitive functions was studied. We assessed changes in learning and memory processes by studying the effects of cysteamine, a compound that decreases somatostatin-like immunoreactivity in the brain, somatostatin and the potent somatostatin analogue, SMS 201-995, on active avoidance behaviour, assessed with a shuttle box apparatus, or on passive avoidance behaviour. Cysteamine induced a loss of the conditioned active avoidance response acquired after 3 weeks of daily trials. The effect was observed 2 h (-29%) and 4 h (-51%) after cysteamine treatment (300 mg/kg s.c.) and disappeared after 24 h. Intracerebroventricular administration of somatostatin or SMS 201-995 to cysteamine-treated rats significantly reversed the cysteamine effects on the conditioned avoidance responses. Similar results were obtained on passive avoidance behaviour. We also investigated the effect of cysteamine treatment on brain somatostatin-sensitive adenylate cyclase. We observed that adenylate cyclase activity in the frontal cortex of cysteamine-pretreated animals was more sensitive to inhibition by the SRIF analogue, SMS 201-995, than it was in control animals. This effect was observed at concentrations of SMS 201-995 that were ineffective in control tissue. These results show that disruption of somatostatinergic transmission affects cognitive functions of rats.

Adenylyl Cyclases↗
PubMed1988

Pertussis toxin pretreatment abolishes dihydropyridine inhibition of calcium flux in the 235-1 pituitary cell line.

In the present study we used 235-1 cells, a prolactin secreting clone derived from a pituitary tumor. In these cells maitotoxin, a calcium channels activator, likely acting on voltage sensitive calcium channels, increases intracellular free calcium measured by Quin 2 technique. Maitotoxin stimulation of calcium flux was inhibited both by nicardipine and verapamil in a dose dependent manner. Pertussis toxin pretreatment does not modify maitotoxin activation of calcium channels, while completely abolishes nicardipine inhibition of maitotoxin induced voltage sensitive calcium channels activation, without affecting verapamil effect. These results suggest a possible involvement of a pertussis toxin sensitive G protein in dihydropyridine inhibition of voltage sensitive calcium channels.

Animals↗
PubMed1988

Adenylate cyclase activity of v-ras-k transformed rat epithelial thyroid cells.

The regulation of adenylate cyclase has been analyzed in normal rat thyroid cells as well as in the same cells transformed by the v-ras-k oncogene. In both cell types the adenylate cyclase complex consists of the two GTP-binding proteins, Gi and Gs, as demonstrated by the specific ADP-ribosylation induced by pertussis and cholera toxin, respectively. The response of adenylate cyclase of the transformed cells to forskolin, pertussis toxin and cholera toxin is attenuated with respect to the control cell line. The thyrotropic hormone (TSH), that acts on normal thyroid cells in culture as a growth factor by stimulating the adenylate cyclase activity, is not able to induce DNA synthesis nor does it stimulate adenylate cyclase in v-ras-k transformed cells.

Adenylate Cyclase Toxin↗