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G Di Renzo

Publications and source records attributed to G Di Renzo.

At least 19 recordsLinked to original sources
PubMed2005

beta-Blockade and increased dyslipidemia in patients bearing Glu27 variant of beta2 adrenergic receptor gene.

In this study, the effects of polymorphisms of the beta(2) and beta(3) adrenergic receptor genes on the occurrence of dyslipidemia and diabetes mellitus in hypertensive patients treated with beta-blockers (atenolol or metoprolol) were evaluated. Patients who gave written informed consent were asked to return for blood sampling for estimation of serum glucose, total cholesterol, HDL, triglycerides and for genotype determination. Genotyping analysis was performed by PCR-RFLP assay. In patients bearing beta(2)AR Glu27 or the beta(3)AR Arg64 variant there was a larger occurrence of hypertriglyceridemia, alone or in combination with elevated cholesterol levels. Furthermore, the beta(2)AR Glu27 variant significantly associates with hypetriglyceridemia in a cumulative fashion. The risk to develop this side effect after beta-blockade was four-fold higher in patients homozygous for the beta(2)AR Glu27 variant as compared to beta(2)AR27Gln allele. This result allows the identification of patients at high risk to develop metabolic complications to chronic beta-blockade treatment.

Adrenergic beta-2 Receptor Antagonists↗
PubMed2003

Caspase-1 inhibitors abolish deleterious enhancement of COX-2 expression induced by HIV-1 gp120 in human neuroblastoma cells.

The human CHP100 neuroblastoma cell line has been shown to provide an useful in vitro model to elucidate the mechanisms underlying HIV-1 gp120 neurotoxicity. Here we report western blotting evidence demonstrating that exposure to a cytotoxic concentration of the viral coat protein up-regulates expression of the inducible isoform of cyclooxygenase (COX-2) in neuroblastoma cells and this seems to be due to the previously observed increase in secreted IL-1beta. In fact, here we show that acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone (Boc-Asp-(OBzl)-CMK), two inhibitors of Interleukin-1 Converting Enzyme (ICE; also referred to as caspase-1), abolish COX-2 expression enhanced by gp120 and consequent cell death. In addition, NS-398, a selective inhibitor of COX-2 activity, affords neuroprotection strengthening the role of COX-2 in the mechanisms of death. In conclusion, the present data support the notion that IL-1beta is the signal through which gp120 elevates COX-2 expression and the latter is strongly implicated in the mechanisms underlying cytotoxicity.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Ethanol exposure inhibits the cytotoxic effect induced by gp120 in CHP100 human neuroblastoma cells.

The aim of present study was to investigate the acute effects of ethanol on cytotoxicity induced by HIV-1 coat protein gp120 in CHP100 human neuroblastoma cell line. We demonstrate that ethanol, within a range of clinically relevant concentrations (15-90 mM) prevents cell death elicited by gp120 (10 pM) in a dose dependent manner. This protective action seems to be mediated by a reduction of free intracellular Ca(2+) levels because ethanol, at concentrations ranging from 0.1-0.5%, is able to decrease gp120-stimulated Ca(2+) uptake up to 24%. Furthermore, our data show an involvement of NO/cGMP messenger system pathway, because ethanol is also able to reduce gp120-stimulated NO release (up to 45%) and cyclic GMP accumulation (up to 73%). These findings suggest that the protective effect of ethanol against gp120-induced cytotoxicity in CHP100 cells underlies a Ca(2+)-activated, NO/cGMP-dependent mechanism.

Calcium↗
PubMed2001

Differential vulnerability of cortical and cerebellar neurons in primary culture to oxygen glucose deprivation followed by reoxygenation.

The effects of glucose and O2 deprivation (OGD) on the survival of cortical and cerebellar neurons were examined to characterize the biochemical mechanisms involved in OGD and OGD followed by reoxygenation. To this aim, neurons were kept for different time periods in a hypoxic chamber with a controlled atmosphere of 95% N(2) and 5% CO2 in a glucose-free medium. After OGD, reoxygenation was achieved by exposing the cells to normal O2 and glucose levels. Neither MTT, an index of mitochondrial oxidative phosphorylation, nor malondialdehyde (MDA) production, a parameter measuring lipid peroxidation, were affected by 1 hr of OGD in cortical neurons. When OGD was followed by 24 hr of reoxygenation, MTT levels were reduced by 40% and MDA was significantly increased, whereas cellular ATP content did not change. Cerebellar granule cells, on the other hand, did not show any reduction of mitochondrial activity after exposure to 1 hr OGD or to 1 hr OGD plus 24 hr of reoxygenation. When OGD was prolonged for 2 hr, a significant reduction of the mitochondrial activity and of cellular ATP content occurred, coupled to a significant MDA increase in cerebellar granule cells, whereas in cortical neurons a reduction of MTT levels after 2 hr OGD was not accompanied by a decrease of cellular ATP content nor by an increase of MDA production. Moreover, 24 hr of reoxygenation further reinforced lipid peroxidation, LDH release, propidium iodide positive neurons and the reduction of ATP content in cerebellar granule cells. The results of the present study collectively show that cortical and cerebellar neurons display different levels of vulnerability to reoxygenation followed by OGD. Furthermore, the impairment of mitochondrial activity and the consequent overproduction of free radicals in neurons were observed for the first time occurring not only during the reoxygenation phase, but already beginning during the OGD phase.

Adenosine Triphosphate↗
PubMed2001

HIV-1 coat protein gp120 stimulates interleukin-1beta secretion from human neuroblastoma cells: evidence for a role in the mechanism of cell death.

1. The role of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the mechanism of cell death induced by the human immunodeficiency virus type 1 (HIV-1) recombinant coat glycoprotein, gp120 IIIB, has been studied in the human CHP100 neuroblastoma cell line maintained in culture. 2. Death of neuroblastoma cells typically elicited by 10 pM gp120 or by human recombinant IL-1beta (10 ng x ml(-1)) has been minimized by the antagonist of IL-1 receptor, i.e. IL-1ra (0.5 and 50 ng x ml(-1), respectively), an endogenous molecule that antagonizes most of the biological actions of IL-1beta, or by an antibody (5 and 50 ng x ml(-1)) which blocks the human IL-1 receptor type I (IL-1RI). 3. ELISA experiments have established that gp120 enhances immunoreactive IL-1beta levels in the culture medium and this is prevented by exposure to the IL-1 converting enzyme (ICE) inhibitor t-butoxycarbonyl-L-aspartic acid benzyl ester-chloromethylketone [Boc-Asp(OBzl)-CMK] used at a concentration (2.5 microM) which significantly (P<0.001) reduces cell death. 4. Death of CHP100 cells induced by gp120 is also prevented by acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK; 10-100 microM), a second inhibitor of ICE, supporting the concept that the viral protein stimulates the conversion of the 31 kDa pro-IL-1beta in to the 17 kDa mature cytokine which is then secreted to cause death. 5. In conclusion, our present data demonstrate that gp120 stimulates the secretion of IL-1beta which then triggers CHP100 neuroblastoma cell death via stimulation of IL-1 receptor type I.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells.

In C6 glioma cells exposed to chemical hypoxia, an increase of extracellular lactate dehydrogenase (LDH) activity, cell death, and intracellular Ca2+ concentration ([Ca2+]i) occurred. Sodium nitroprusside (SNP), a nitric oxide donor and an iron-containing molecule, reduced chemical hypoxia-induced LDH release and cell death. These effects were counteracted by bepridil and by 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), two specific inhibitors of the Na+-Ca2+ exchanger. SNP also increased the activity of the Na+-Ca2+ exchanger as a Na+ efflux pathway, stimulated by Na+-free conditions and evaluated by monitoring [Ca2+]i in single cells. In addition, SNP produced a further increase of chemical hypoxia-elicited [Ca2+]i elevation, and this effect was blocked by bepridil. Chemical hypoxia-evoked cell death and LDH release were counteracted by the ferricyanide moiety of the SNP molecule, K3Fe(CN)6, and by ferric chloride (FeCl3), and this effect was counteracted by CB-DMB. In addition, the iron ion chelator deferoxamine reversed the protective effect exerted by SNP on cell injury. Collectively, these findings suggest that the protective effect of SNP on C6 glioma cells exposed to chemical hypoxia is due to the activation of the Na+-Ca2+ exchanger operating as a Na+ efflux-Ca2+ influx pathway induced by iron present in the SNP molecule.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Pharmacological blockade of ERG K(+) channels and Ca(2+) influx through store-operated channels exerts opposite effects on intracellular Ca(2+) oscillations in pituitary GH(3) cells.

In the present study, the effects on intracellular calcium concentration ([Ca(2+)](i)) oscillations of the blockade of ether-a-go-go-related gene (ERG) K(+) channels and of Ca(2+) influx through store-operated channels (SOC) activated by [Ca(2+)](i) store depletion have been studied in GH(3) cells by means of a combination of single-cell fura-2 microfluorimetry and whole-cell mode of the patch-clamp technique. Nanomolar concentrations (1-30 nM) of the piperidinic second-generation antihistamines terfenadine and astemizole and of the class III antiarrhythmic methanesulfonanilide dofetilide, by blocking ERG K(+) channels, increased the frequency and the amplitude of [Ca(2+)](i) oscillations in resting oscillating GH(3) cells. These compounds also induced the appearance of an oscillatory pattern of [Ca(2+)](i) in a subpopulation of nonoscillating GH(3) cells. The effects of ERG K(+) channel blockade on [Ca(2+)](i) oscillations appeared to be due to the activation of L-type Ca(2+) channels, because they were prevented by 300 nM nimodipine. By contrast, the piperazinic second-generation antihistamine cetirizine (0.01-30 microM), which served as a negative control, failed to affect ERG K(+) channels and did not interfere with [Ca(2+)](i) oscillations in GH(3) cells. Interestingly, micromolar concentrations of terfenadine and astemizole (0.3-30 microM), but not of dofetilide (10-100 microM), produced an inhibition of the spontaneous oscillatory pattern of [Ca(2+)](i) changes. This effect was possibly related to an inhibition of SOC, because these compounds inhibited the increase of [Ca(2+)](i) achieved by extracellular calcium reintroduction after intracellular calcium store depletion with the sarcoplasmic or endoplasmic reticulum calcium ATPase pump inhibitor thapsigargin (10 microM) in an extracellular calcium-free medium. The same inhibitory effect on [Ca(2+)](i) oscillations and SOC was observed with the first-generation antihistamine hydroxyzine (1-30 microM), the more hydrophobic metabolic precursor of cetirizine. Collectively, the results of the present study obtained with compounds that interfere in a different concentration range with ERG K(+) channels or SOC suggest that 1) ERG K(+) channels play a relevant role in controlling the oscillatory pattern of [Ca(2+)](i) in resting GH(3) cells and 2) the inhibition of SOC might induce an opposite effect, i.e., an inhibition of [Ca(2+)](i) oscillations.

Animals↗
PubMed1999

In the neuronal cell line SH-SY5Y, oxidative stress-induced free radical overproduction causes cell death without any participation of intracellular Ca(2+) increase.

Adding the membrane-permeant oxidant tert-butylhydroperoxide (t-BOOH) to the incubation medium, in SH-SY5Y human neuroblastoma cells, induced a marked and progressive concentration-dependent (300, 500 and 1000 microM) increase of free radical production, as evaluated by the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and of the intracellular Ca(2+) ion concentrations [Ca(2+)](i). The removal of extracellular Ca(2+) ions did not prevent t-BOOH-induced [Ca(2+)](i) elevation, whereas the intracellular Ca(2+) ion chelator 1,2-bis(o-aminophenoxy) ethane-N,N, N',N'-tetraacetic acid (BAPTA) (10 microM) was shown to be effective. Both t-BOOH-induced free radical formation and the [Ca(2+)](i) increase were completely prevented by the peroxyl scavenger alpha-tocopherol (50 microM). t-BOOH induced a time-dependent SH-SY5Y cell injury, monitored by a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay (approximately 25% at 1 h, 50% at 3 h, 80% at 5 h) and by fluorescein diacetate (FDA)-propidium iodide (PI) fluorescent staining. The entity of t-BOOH-induced cell damage was the same both in the absence and in the presence of the intracellular Ca(2+) ion chelator BAPTA. By contrast, the peroxyl scavenger alpha-tocopherol (50 microM) completely prevented cell injury due to oxidative stress. Finally, superoxide dismutase (SOD) (500 ng/ml) caused a 30% reduction of t-BOOH-induced 2', 7'-dichlorofluorescein (DCF) fluorescence, whereas it did not modify the extent of cell injury produced by the oxidant. Collectively, the results of the present study demonstrated that in SH-SY5Y human neuroblastoma cells, the rise of [Ca(2+)](i) which occurs during oxidative stress is not involved in cell injury. Therefore, oxidative stress-induced cell death may be exclusively attributed to free radical overproduction.

Calcium↗
PubMed1999

Studies on maitotoxin-induced intracellular Ca(2+) elevation in chinese hamster ovary cells stably transfected with cDNAs encoding for L-type Ca(2+) channel subunits.

The aim of the present study was to characterize the role played by different L-type Ca(2+) channel subunits in [Ca(2+)](i) increase induced by maitotoxin (MTX). In the presence of 5 mM extracellular K(+), MTX (0.01-0.5 ng/ml) induced a significant concentration-dependent increase in Fura-2-monitored [Ca(2+)](i) in single Chinese hamster ovary (CHO) cells expressing the alpha(1c) (CHOCalpha9 cells) or the alpha(1c)beta(3)alpha(2)delta (CHOCalpha9beta3alpha2/delta4 cells) subunits of voltage-gated Ca(2+) channels (VGCCs), whereas the effect was much reduced in wild-type CHO cells lacking VGCCs. In addition, MTX effect on CHOCalpha9, CHOCalpha9beta3alpha2/delta4, and GH(3) cells (0.01-0.1 ng/ml) was inhibited by the selective L-type Ca(2+) channel entry-blocker nimodipine (10 microM); a nimodipine-insensitive component was still present, particularly at high (>1 ng/ml) toxin concentrations. In CHOCalpha9beta3alpha2/delta4 cells, depolarizing concentrations of extracellular K(+) (55 mM) reinforced the [Ca(2+)](i) increase induced by MTX (0.1 ng/ml), and this effect was prevented by nimodipine (10 microM). Finally, patch-clamp experiments in CHOCalpha9beta3alpha2/delta4 cells showed that low MTX concentrations (0.03 ng/ml) induced the occurrence of an inward current at -60 mV, which was completely prevented by Cd(2+) (100 microM) and by nimodipine (10 microM), whereas the same dihydropyridine concentration (10 microM) failed to prevent the electrophysiological effects of a higher toxin concentration (3 ng/ml). In conclusion, the results of the present study showed that MTX-induced [Ca(2+)](i) elevation involves two components: 1) an action on L-type VGCCs at the pore-forming alpha(1c) subunit level, which is responsible for the greatest rise of [Ca(2+)](i); and 2) a VGCC-independent mechanism that is present both in excitable and in nonexcitable cells and is responsible for a lower elevation of [Ca(2+)](i).

Animals↗
PubMed1997

Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment.

Cabergoline (CAB), a new, potent, and long-lasting PRL-lowering agent, was shown to be effective in tumoral hyperprolactinemia. The aim of this study was to investigate the effectiveness of CAB in patients with prolactinoma proven to be resistant to bromocriptine (BRC) and quinagolide (CV 205-502). Twenty-seven patients (19 macro- and 8 microprolactinomas) were treated with CAB at a weekly dose of 0.5-3 mg for 3-22 months. All patients were previously shown to be resistant to BRC, and 20 of them were resistant to CV 205-502 as well. Basal serum PRL levels before CAB treatment ranged from 108-3500 micrograms/L in macroprolactinomas and from 64-205 micrograms/L in microprolactinomas. Gonadal failure was present in all patients, whereas symptoms of tumor expansion, such as visual field defects and headache, were present in 10 of 27 patients. Eight macroprolactinomas had previously undergone surgery and/or radiotherapy. CAB treatment normalized serum PRL levels in 15 of 19 macroprolactinomas and in all 8 microprolactinomas. In 3 of the remaining 4 patients it caused a notable decrease in prolactinemia (89%, 80.5%, and 68.7% of the baseline). Only 1 patient was withdrawn from CAB therapy after 3 months at the weekly dose of 2 mg due to the absence of any significant clinical, hormonal, or radiological improvement. Gonadal function was restored in 18 of 27 patients, galactorrhea disappeared in 5 of 6 women, and headache improved in 7 of 8 patients. A significant tumor shrinkage was detected by computed tomography and/or magnetic resonance imaging in 9 macroprolactinomas and 4 microprolactinomas. CAB was well tolerated by all patients, except 6 who referred slight and short-lasting nausea, postural hypotension, abdominal pain, dizziness, and sleepiness at the beginning of treatment. In particular, CAB was well tolerated by 19 patients previously shown to be poorly tolerant to BRC and CV 205-502. In conclusion, CAB may represent, at the moment, the only successful therapy for prolactinoma-bearing patients resistant to BRC and CV 205-502, as it normalized PRL levels in 22 of 27 patients, reduced tumor size in 13 of 27 patients, and improved clinical symptoms in 25 of 27 patients in the present study.

Adolescent↗
PubMed1996

Felbamate inhibits cloned voltage-dependent Na+ channels from human and rat brain.

The novel antiepileptic and neuroprotective drug felbamate (1 mM) caused a marked inhibition of voltage-dependent Na+ currents expressed in Xenopus oocytes upon injection of the cRNA encoding alpha-subunits from rat and human brain. This inhibition was present only if felbamate was perfused on the intracellular side of the membrane. In addition, felbamate seems to preferentially bind to and stabilize the inactivated state of the channel, resembling the action of local anesthetics. This study provides an additional mechanism by which felbamate might exert its wide-spectrum anticonvulsant and neuroprotective action.

Animals↗
PubMed1995

Role of the Na(+)-Ca2+ and Na(+)-H+ antiporters in prolactin release from anterior pituitary cells in primary culture.

2',4'-dimethylbenzamilamiloride (DMB), a somewhat selective inhibitor of the Na(+)-Ca2+ exchanger, in concentrations of 10, 30 and 100 microM did not produce any significant effect on baseline prolactin release from anterior pituitary cells in primary culture. When prolactin secretion was stimulated by the inhibitor of the Na(+)-K(+)-ATPase, ouabain, that activates the Na(+)-Ca2+ exchanger as a Ca(2+)-influx pathway, DMB was able to produce inhibition of prolactin secretion. 5-(N,N-hexamethylene) amiloride (HMA), another amiloride analog which specifically inhibits the Na(+)-H+ antiporter and has no inhibitory activity on the Na(+)-Ca2+ exchanger, at the concentrations of 0.1, 1 and 10 microM, did not affect basal prolactin release whereas it significantly reduced prolactin release stimulated by thyrotropin releasing hormone (TRH) (1 microM). These results suggest that the Na(+)-Ca2+ antiporter is involved in the process of prolactin release elicited by the inhibition of the Na(+)-K(+)-ATPase whereas the Na(+)-H+ antiporter is involved in the prolactin secretion elicited by TRH.

Amiloride↗
PubMed1995

The A1 agonist CCPA reduced bisoxonol-monitored membrane potential depolarization elicited by high K+ in cerebrocortical nerve endings.

In this study the effect of the A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA) on bis(1,3-diethylthiobarbituric acid)trimethine oxonol (bisoxonol)-monitored membrane potential in cerebrocortical nerve endings was evaluated. CCPA (30, 100 and 300 microM) caused a dose-dependent decrease of high K(+)- and veratridine-induced membrane depolarization. This decrease was counteracted by the A1-specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (30-100 microM). On the contrary, the A2 receptor antagonist 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolol-[1,5-c]quinazol ine-5- imine (CGS 15943) was unable to interfere with the lowering effect exerted by CCPA (100 microM) on K(+)-elicited membrane depolarization. Finally, the A2 receptor agonist 2-[p-(2-carboxyethyl)phenethylamine]-5'-N-ethylcarboxamidoadenosine (CGS 21680) did not induce any modification of K(+)-induced membrane depolarization. The results of the present study suggest that K(+)-induced membrane depolarization in cerebrocortical brain nerve endings may be modulated by A1 receptors.

Adenosine↗
PubMed1994

Relationship between time of activation of phospholipase C-linked plasma membrane receptors and reloading of intracellular Ca2+ stores in LAN-1 human neuroblastoma cells.

The effect of sequential stimulation of different inositol (1,4,5)-trisphosphate (IP3)-linked receptors on the functioning of intracellular Ca2+ stores was evaluated in single LAN-1 human neuroblastoma cells by means of fura-2 microfluorimetry. Homologous restimulation both in the absence and in the presence of extracellular Ca2+ with endothelin-1 (ET-1), Lys-bradykinin (BK), and ATP did not elicit an intracellular Ca2+ increase, whereas a [Ca2+]i elevation after carbachol (CCh) re-exposure was obtained only in the presence of extracellular Ca2+. Since thapsigargin and ionomycin, in the absence of extracellular Ca2+, were still able to release Ca2+ after ET-1, BK, and ATP but not after CCh, it can be argued that in the first case the stores were not completely depleted. This evidence was also confirmed by the fact that LAN-1 cells, sequentially exposed in different order to ET-1, BK, ATP, and upon extracellular Ca2+ removal, showed an increase of [Ca2+]i although progressively reduced in magnitude. By contrast, when CCh was perfused as the first agonist, it completely precluded any further Ca2+ mobilization by the other three agonists. In addition, the lack of potentiation of the Ca2+ response when BK and ET-1 were superfused together and the potentiation of Ca2+ response elicited by ET-1 after BK, when the plasma membrane Ca2+ efflux pathways were blocked by lanthanum during the first agonist exposure, indicated that LAN-1 cells can recycle cytoplasmic Ca2+ when exposed to ET-1, BK, ATP but not when exposed to CCh. This inhibitory effect of CCh (perfused for 90 s) on Ca2+ refilling was strictly dependent on the time of receptor occupancy since the exposure to CCh for a shorter period (15 s) produced the same effect on Ca2+ refilling when ET-1, BK, and ATP were perfused, as first agonist, for 90 s. Furthermore, the entity of Ca2+ refilling after 15 s of BK receptor occupancy was similar to that observed after 90 s. This seems to suggest that the receptors for ET-1, BK, and ATP maintain the transductional mechanisms in an activated state for a time shorter than the time of receptor occupancy. This was confirmed by the fact that IP3 levels during a 90-s BK exposure fell to prestimulated value within 30 s, whereas after CCh they reached a sustained plateau phase, after the peak.

Calcium↗
PubMed1994

Appearance of depolarization- and maitotoxin-induced [Ca2+]i elevation in single LAN-1 human neuroblastoma cells on exposure to retinoic acid.

LAN-1 is a human neuroblastoma cell line that, in the undifferentiated state, does not respond to membrane depolarization with an elevation of [Ca2+]i, monitored by fura-2 single-cell microfluorimetry. The exposure of LAN-1 cells to the differentiating agent retinoic acid induced the appearance of [Ca2+]i elevation elicited by 55 mM K+. Maitotoxin, a putative activator of voltage-sensitive Ca2+ channels, did not evoke an elevation of [Ca2+]i in undifferentiated LAN-1 cells, but produced a marked and sustained increase in [Ca2+]i when superfused in retinoic acid-treated cells. Both high K(+)- and maitotoxin-induced [Ca2+]i elevation in retinoic acid-differentiated LAN-1 cells was reversed by the lanthanide Gd3+, an inorganic Ca(2+)-entry blocker, and by the snail toxin omega-conotoxin GVIA, which interacts with the N subtype of voltage-sensitive Ca2+ channels. In contrast, both Bay K 8644 and nimodipine, dihydropyridines that selectively activate or block, respectively, the L-channel subtype, were completely ineffective. The tumor promoter phorbol 12-myristate 13-acetate (100 nM), a protein kinase C activator, inhibited the elevation of [Ca2+]i due to Ca2+ influx elicited by membrane depolarization. K(+)-induced [Ca2+]i elevation appeared 24 h after the addition of retinoic acid and reached the highest magnitude after 72 h. Furthermore, 8 days after the removal of the differentiating agent from the culture medium, the high K(+)-induced increase of [Ca2+]i was still present.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies.

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 micrograms sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mumol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factor-I levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Individual housing modulates daily rhythms of hypothalamic catecholaminergic system and circulating hormones in adult male rats.

Circadian rhythms of hypothalamic catecholamines and their metabolites and of prolactin and corticosterone circulating hormones were determined over 24 h in group-housed (six per cage; control) and individually housed, 90-day-old male albino rats adapted to a 12:12 light/dark cycle. After 5 weeks of adaptation, in individually housed rats, norepinephrine (NE) turnover increased, since lower NE (p < 0.01) and higher MOPEG metabolite (p < 0.01) levels were measured. As concerns the dopaminergic system, individually housed rats increased both dopamine (DA) synthesis and turnover as revealed by higher DOPAC (p < 0.01) and HVA (p < 0.05) metabolites without modification of DA levels. Moreover, in individually housed rats, corticosterone (p < 0.01) and prolactin (p < 0.05) mean levels were higher than in the control group.

3,4-Dihydroxyphenylacetic Acid↗