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Biomedical subjects

M Parenti

Publications and source records attributed to M Parenti.

At least 55 records · Page 3Linked to original sources
PubMed1993

In situ hybridization reveals specific increases in G alpha s and G alpha o mRNA in discrete brain regions of morphine-tolerant rats.

In situ hybridization histochemistry has been used to detect the basal distribution of mRNA encoding the alpha subunit of Gs, Go and Gi2 proteins throughout the rat brain. Based on these data we investigated the effect of chronic morphine on the content of these G protein alpha subunits mRNA. We observed an increase in the expression of alpha s and alpha o messages of chronically morphine-treated animals, while no changes were seen in alpha i2 mRNA. Specifically a 30% increase in expression for alpha s was seen only in the paraventricular nucleus of hypothalamus and a 20% elevation for alpha o was detected in the claustrum and endopiriform nucleus. Immunoblotting analysis was used to correlate the changes in alpha s and alpha o messages with equivalent changes in protein levels. Chronic morphine significantly increased alpha s amounts in the hypothalamus (70%), and produced a minor elevation (30%) in G alpha o levels in the olfactory area. Our results indicate that in discrete brain regions altered G protein expression is part of the adaptive changes underlying opiate tolerance.

Animals↗
PubMed1993

Pharmacological characterization of the 5-hydroxytryptamine receptor coupled to adenylyl cyclase stimulation in human brain.

Recently, a 5-hydroxytryptamine (5-HT) receptor has been described, whose pharmacology was distinct from that of the already known serotonergic receptors, so that it has been called 5-HT4. Because the lack of a high affinity radioligand, the identification of this receptor depends entirely on functional pharmacological analysis. Its stimulation leads to an increase in cyclic AMP accumulation in mouse embryo colliculi neurons, in guinea pig hippocampus and in human heart. We studied the effect of two indoleamines, 5-HT and 5-methoxytryptamine (5-MeO-T), and a benzimidazolone derivative, BIMU 8, in stimulating basal adenylyl cyclase activity in human frontal cortex, and characterized the receptor subtype involved. In membranes prepared from this tissue, 5-HT, 5-MeO-T and BIMU 8 dose-dependently stimulated (13-25%) the basal enzyme activity (220 pmoles cyclic AMP/min/mg protein). 5-MeO-T behaved as a full agonist, BIMU 8 elicited about 60% of the maximal 5-HT effect. The selective 5-HT1A agonist 8-OH-DPAT, was devoid of any stimulating activity. ICS 205-930, a low affinity 5-HT4 receptor antagonist, completely reversed the effect of all three agonists at high concentrations. Therefore, the present data are consistent with the 5-HT-mediated stimulation of adenylyl cyclase in human frontal cortex resulting by the activation of a 5-HT4 receptor subtype.

5-Methoxytryptamine↗
PubMed1993

Growth hormone secretion is differently affected in genetically obese male and female rats.

Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate the function of hypothalamic GHRH and somatostatin and of pituitary receptors for these neurohormones as assessed by the effectiveness of GHRH and somatostatin on adenylate cyclase (AC) activity. Baseline GH secretion of pituitaries obtained from male and female obese rats was not different and similar to that present in lean counterparts. Stimulation with 10(-7) M GHRH elicited a significantly lower GH secretion from the pituitaries of obese male rats but induced a similar GH secretion from the pituitaries of lean and obese female rats. In these pituitaries, GH concentration was similar in obese versus lean male and female rats [corrected]. A sex-related difference was also evidenced when plasma concentrations of somatomedin C (IGF-I) were evaluated. Obese male rats had lower IGF-I concentrations than lean counterparts, while this was not the case for obese versus lean female rats. Evaluation of AC activity following GHRH disclosed a lower activation in obese than in lean male rats, whereas in the females the enzyme activation was higher in obese than in lean animals. Conversely, the inhibitory effect of somatostatin on forskolin-stimulated AC was similar in pituitary membranes of obese and lean rats of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1993

Effect of ethanol exposure on voltage-dependent calcium channels in in vitro cellular models.

Chronic ethanol exposure alters calcium movements and the number of dihydropyridine (DHP) binding sites in the animal brain and in cultured neural cell lines. The present study investigates the effect of ethanol treatment on dihydropyridine- and omega-conotoxin (CgTx)- labelled calcium channels in undifferentiated and differentiated NG 108-15 cells. Following differentiation, the binding of [3H] -PN 200-110 increased by 48% while [125I]-CgTx binding increased by six fold. In accordance with data in the literature, undifferentiated cells exposed to ethanol (3 days) showed a large increase (70%) in DHP binding sites. In contrast, CgTx binding sites were unmodified by the treatment. Using differentiated cells, ethanol exposure induced a significant decrease (53%) in CgTx binding sites without altering those labelled by PN 200-110 (isradipine). These findings indicate that the effect of ethanol exposure on calcium channels may be dependent on the type of channel considered and on the status of the cells treated.

Animals↗
PubMed1993

Aspects of the neuroendocrine control of growth hormone secretion in ageing mammals.

In aged animals and humans the pulsatile secretion of growth hormone (GH), the mean amounts of GH released over 24 h, and the response of GH to the administration of GH-releasing hormone (GHRH) are lower than in young adults. Pituitary somatotrophic cells in old male and female rats show an impaired responsiveness to GHRH, and the reduced secretion of GH in vitro is linked with a diminished stimulation of adenylate cyclase by GHRH. Pretreatment with GHRH in vivo decreases the high basal adenylate cyclase activity in old male rats. This pretreatment does not affect the rise of adenylate cyclase concentration in these rats that is subsequently induced by GHRH administration in vitro. However, it does induce a small rise in adenylate cyclase concentration in old female rats. In young rats of either sex the same GHRH schedule does not alter adenylate cyclase activity, but it does reduce the effectiveness of subsequent acute exposure to GHRH to stimulate enzymatic activity. Short-term administration of GHRH in some aged subjects increases the response of GH to a subsequent acute challenge with GHRH. However, primary or secondary alterations in somatotrophic cells are also present in aged mammals, such as a reduction in the number of GH-immunoreactive structures or post-receptor alterations. In aged rats, major alterations in brain neurotransmitters and neuropeptides are present in hypothalamic and extrahypothalamic structures, especially in catecholaminergic and acetylcholinergic neurones. These alterations are probably due to defects in neurosecretory GHRH and somatostatin neurones. GHRH synthesis is impaired in the hypothalamus of senescent male rats, as shown by a reduction in GHRH mRNA levels and GHRH-like immunoreactivity. Although the expression of somatostatin seems to decrease with age in the rat hypothalamus, secretion and activity of this hormone is increased, resulting in an altered relationship between GHRH and somatostatin gene expression and secretion. Catecholamines induce GH release in most animal species by stimulating GHRH neurones and inhibiting somatostatin-releasing neurones. Acetylcholine stimulates GH release via muscarinic receptors, and thus inhibits the effect of somatostatin neurones. In male rats of various ages, except very young rats, systemic administration of pilocarpine, an agonist of muscarinic receptors, potentiates the GH response to GHRH during the entire lifespan.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Cyclosporine renal cortical vasoconstriction measured by colour Doppler imaging in kidney transplantation.

Important side-effects limit the use of cyclosporine A (CSA), the most insidious of which is nephrotoxicity, which manifests as a preglomerular arteriolar vasoconstriction causing a reduction in glomerular filtration rate (GFR) and renal plasma flow (RPF). This condition is initially purely functional, but with time can become anatomic and irreversible. In clinical practice we lack suitable methods for evaluating CSA vasoconstriction. Our present knowledge is based on indirect information obtained from repeated measurerments of plasma creatinine levels and from blood concentrations of the drug. Sometimes more complex and non-routine tests, such as the evaluation of GFR and RPF, or invasive methods, such as renal biopsy, are also employed. In this study we used the colour-Doppler technique to measure directly the vascular effects of CSA in patients with transplanted kidneys, evaluating changes in blood flow at the hilus and on the cortex of the kidney when the drug was at trough or peak levels.

Adult↗
PubMed1992

Lipid, lipoprotein, and apolipoprotein assessment during an 8-wk very-low-calorie diet.

The influence of a very-low-calorie diet (VLCD) on lipid pattern is controversial. To evaluate the long-term effect of semistarvation on lipid patterns, a group of severely obese patients [aged 37 +/- 12 y, body mass index (BMI) 40.0 +/- 0.9] underwent a VLCD for 8 wk. Total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), triglycerides (TGs), apolipoproteins A1 (apo A1) and B (apo B) were analyzed every week. TC (6.07 +/- 0.23 vs 5.53 +/- 0.25 mmol/L, P less than 0.0008), HDL-C (mmol/L 1.26 +/- 0.06 vs 1.04 +/- 0.05 mmol/L, P less than 0.0001), TGs (1.46 +/- 0.19 vs 1.06 +/- 0.10 mmol/L, P less than 0.0008), and apo A1 (1.57 +/- 0.06 vs 1.32 +/- 0.06 g/L, P less than 0.0002) decreased, whereas LDL-C and apo B showed a biphasic behavior: they significantly fell during the first 3 wk, but during the last weeks returned to their initial values.

Adult↗
PubMed1992

Pancreatic exocrine carcinoma producing adrenocorticotropic hormone.

A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation.

ACTH Syndrome, Ectopic↗
PubMed1992

G protein modulation of omega-conotoxin binding sites in neuroblastoma x glioma NG 108-15 hybrid cells.

Electrophysiological evidence shows that voltage-dependent calcium channel (VDCC) activity can be regulated by a large number of neurotransmitters. In particular, guanine nucleotide binding regulatory protein (G protein)-mediated inhibitory modulation of the channel activity has been deduced from evidence that GTP analogues and purified G proteins are able to mimic this effect. The G proteins involved are pertussis toxin (PTx) sensitive. The purpose of the present study was to investigate, using biochemical techniques, whether G protein activation modulates the recognition site for omega-conotoxin GVIA (CgTx), a peptide neurotoxin that selectively labels a population of high-threshold VDCC. Undifferentiated and differentiated (1 mM dibutyryl cyclic AMP, 4 days) NG 108-15 cells were used. In both crude cellular extracts specific binding of 125I-CgTx was characterized. Differentiation induced a sixfold increase in the number of binding sites and doubled the KD value. The in vitro addition of guanylylimidodiphosphate (GMP-PNP; a nonhydrolyzable analogue of GTP) to extracts prepared from differentiated cells reduced the 125I-CgTx binding by 48%. This effect, observed in undifferentiated cells as well, was also caused by other triphosphate guanine nucleotides, such as GTP, but not by guanosine 5'-O-(2-thiodiphosphate) or adenine nucleotides. Treatment of the cells with PTx prevented the GMP-PNP effect. Moreover, the results obtained after preincubation with specific antisera raised against the alpha subunits of Gi1-2 and Go suggest that Go is the G protein responsible for the observed effect.

Animals↗
PubMed1991

Pertussis toxin-sensitive G-protein mediates galanin's inhibition of scopolamine-evoked acetylcholine release in vivo and carbachol-stimulated phosphoinositide turnover in rat ventral hippocampus.

The effects of intracerebroventricular (i.c.v.) injections of pertussis toxin were investigated on the inhibitory action of galanin on acetylcholine release and phosphoinositide breakdown stimulated by muscarinic agents in rat ventral hippocampus. Pertussis toxin (0.6 micrograms, i.c.v., 96 h) counteracted the in vitro inhibitory effect of galanin (3.1 nmol) on phosphoinositide breakdown stimulated by carbachol without altering the stimulatory action of the cholinergic agonist on signal transduction, in miniprisms from rat ventral hippocampus. Pertussis toxin also abolished the in vivo effect of galanin on scopolamine-stimulated acetylcholine release in vivo but did not affect basal acetylcholine release. The results indicate that pertussis toxin-sensitive G-protein(s) mediates the galanin receptor regulation of pre- and postsynaptic cholinergic functions in the ventral hippocampus.

Acetylcholine↗
PubMed1991

Pertussis toxin pretreatment affects opiate/nonopiate and stress-induced analgesia differently.

Intracerebroventricular injection of pertussis toxin (PTX, 1 microgram/rat) six days before the hot plate test abolished analgesia induced by central morphine. The toxin did not affect analgesia evoked by central neurotensin or ASU 1-7 eel calcitonin. PTX pretreatment also attenuated footshock-induced analgesia (FSIA) delivered to all four paws. When the shock was restricted to the front paws, PTX consistently lowered postshock tail flick latencies, but did not reduce analgesia resulting from shock delivered to the hind paws. It thus appears that PTX-sensitive G-proteins are an essential transduction step needed to initiate the molecular events underlying opiate analgesia evoked by either morphine or shock. In contrast, the signal transduction mechanism subsequent to the stimulation of neurotensin or calcitonin receptors, and to the nonopiate FSIA, appears not to involve PTX-sensitive G-proteins.

Animals↗
PubMed1991

Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland.

The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21-23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1990

Pertussis toxin modifies the effect of central morphine on rat intestinal motility.

To find whether the antipropulsive effect of morphine administered intracerebroventricularly (i.c.v.) depends on a G-protein-mediated mechanism, we studied the effect of i.c.v. pertussis toxin (PTX) pretreatment on morphine-induced inhibition of intestinal motility. The influence of PTX was evaluated on intestinal transit (charcoal meal test) and by monitoring of intestinal myoelectrical activity. The antitransit effect of morphine (10 micrograms/rat) was antagonized by about 70% 3, 6, 9 and 12 days after PTX pretreatment (1 microgram/rat) and it was partially restored after 25 days. I.c.v. morphine abolished the regular appearance of the myoelectric migrating complex (MMC) recorded in the rat jejunum and this effect was completely antagonized by PTX pretreatment. When morphine was injected 25 days after PTX, it significantly reduced MMC frequency, confirming the partial recovery seen in the transit experiments. The pertussis toxin-catalyzed ADP ribosylation of a 39-41 kDa substrate in membranes prepared from hypothalamus and midbrain of rats injected with toxin 6 days before was strongly reduced as compared to the controls. On the contrary, after 25 days, ADP ribosylation was the same in treated and control rats. Thus the antipropulsive effect of central morphine could be initiated at receptor sites which interact with G-protein substrates of pertussis toxin.

Adenosine Diphosphate↗
PubMed1990

Diabetic retinopathy in chronic pancreatitis.

Using fluorescein angiography, we studied the prevalence and characteristics of diabetic retinopathy in 40 patients with chronic pancreatitis complicated by diabetes and in 40 type 1 diabetics with comparable duration of diabetes. Retinopathy was found in 19 pancreatitis patients (47.5%) and in 20 type 1 diabetic patients (50%); it was background, minimal, or mild to moderate, without impairment of visual function, in all 19 pancreatitis patients and in 17 of the 20 type 1 diabetics. In the remaining three idiopathic diabetics, retinopathy was background of severe degree in two and proliferative, with impairment of vision, in one. No differences between patients with and without retinopathy were observed in fasting blood glucose, glycosylated hemoglobin, serum cholesterol, or triglyceride levels. The only significant difference (p less than 0.001) was the greater duration of diabetes in patients with retinopathy when compared with those without it (10.8 +/- 5.7 vs. 5.2 +/- 3.9 yr in pancreatitis patients; 11.2 +/- 5.0 vs. 5.1 +/- 3.5 yr in type 1 diabetics; mean +/- SD). Contrary to what is generally believed, the results indicate that the risk of retinopathy and the characteristics of this complication in patients with chronic pancreatitis and secondary diabetes are similar to those in patients with idiopathic diabetes.

Blood Glucose↗