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Biomedical subjects

M C Rubio

Publications and source records attributed to M C Rubio.

At least 91 records · Page 5Linked to original sources
PubMed1987

The aziridinium derivative of DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) accelerates the beating rate of isolated rat atria by enhancing the spontaneous release of noradrenaline.

The aziridinium derivative of the compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (az-DSP4) depletes endogenous noradrenaline stores and exerts neurotoxic actions on noradrenergic neurons. These effects are persistent in the central nervous system and transient in the periphery. To determine if transmitter release plays a role in the noradrenaline depletion caused by az-DSP4, the action of the compound was studied in isolated and spontaneously beating rat atria. 1. az-DSP4 enhanced atrial beating rate when present in the incubation medium at concentrations ranging from 10(-7) M to 10(-4) M but at 10(-3) M decreased that rate below basal levels. 2. Preincubation of atria for 30 min with the noradrenaline uptake blocker desimipramine (DMI, 10(-6) M) or with the beta-blocker propranolol (10(-7) M), abolished the positive chronotropic action of az-DSP4. 3. The rate-accelerating effect of az-DSP4 could be prevented by pretreating the rats with reserpine (5 mg/kg i.p. 24 h) or enhanced by pargyline pretreatment (100 mg/kg i.p. 18 h). 4. az-DSP4 stimulated the spontaneous efflux of tritium from the isolated atria previously labeled with 3H-noradrenaline (4 X 10(-7) M), an increase that was mainly accounted for by DOPEG. 5. COMT and MAO activities in atria homogenates were inhibited by az-DSP4 in a concentration-dependent manner. However, MAO inhibition did not result in a change of the metabolic pattern as could be expected. 6. The results obtained indicate that az-DSP4 enhances the rate of spontaneous beating of isolated rat atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of TRH on hypothalamic catecholaminergic and serotoninergic neurons.

The in vivo and in vitro effects of TRH on tyrosine hydroxylase activity and on endogenous levels of noradrenaline as an index of noradrenergic neurons activity were studied in rat hypothalamus. The hydroxylation of tryptophan and the liberation of 5-hydroxyindole acetic acid were analyzed as an index of serotoninergic activity. TRH had no effect on tyrosine hydroxylase from hypothalamic homogenates in concentrations up to 100 ng/ml. Neither was the hydroxylation of tyrosine in intact hypothalamus. The TRH (4 micrograms/kg) decreased 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine accumulation after 10 min, and no effect on serotonin and noradrenaline concentrations was observed. TRH decreased endogenous levels of 5-hydroxyindole acetic acid by 35%. Thus, the results show that TRH or TSH might play a role in a short-loop feedback action involving catecholaminergic and serotonergic nerve terminals that regulate the liberation of TRH.

Animals↗
PubMed1987

Comparative activity of ceftizoxime against aminoglycoside-resistant aerobic gram-negative bacilli.

The in vitro activity of ceftizoxime was compared with that of other beta-lactam antibiotics against 331 aminoglycoside (AG)-resistant clinical isolates. Two hundred and six AG-resistant, beta-lactamase producing, R-plasmid harbouring Enterobacteriaceae strains had MICs ranging from 0.0125 to 0.063 mg/l. AG-resistant Escherichia coli (36 strains) and Klebsiella pneumoniae (19) had MIC 90 values of 8 mg/l. Proteus rettgeri and P. vulgaris as well as Morganella morganii, resistant to several AGs, had MICs ranging from 0.5 to 4 mg/ml. Against all six isolates of AG-resistant Salmonella enteritidis the MIC90 was 0.5 mg/l. Twenty-seven strains of Serratia marcescens, most of which were resistant to beta-lactam and AG antibiotics, had MICs ranging from 0.5 to 8 mg/l. The AG-resistant strains of Enterobacteriaceae producing several AG-modifying enzymes (AAC(3); AAC(2'); AAC(6'); APH(3')) showed MICs ranging from 0.6 to 4 mg/l. Against 10 AG-resistant strains of Pseudomonas aeruginosa producing AAC(3), AAC(6') and APH(3') enzymes, the MICs ranged from 16 to 64 mg/l. In conclusion, ceftizoxime was equally or more active than cefotaxime, cefoperazone, ceftazidime and moxalactam against AG-resistant E. coli, Klebsiella, Morganella, Proteus, Serratia, Salmonella and R-plasmid harbouring Enterobacteriaceae. Ceftizoxime was less active than cefotaxime, moxalactam and ceftazidime against P. aeruginosa.

Aminoglycosides↗
PubMed1986

Acute and chronic effects of lithium chloride on GABA-ergic function in the rat corpus striatum and frontal cerebral cortex.

The acute (1 h, i.p.) and chronic (14 days, p.o.) effects of LiCl treatment upon GABA-ergic neurons were studied in the rat corpus striatum and frontal cerebral cortex. One hour after a single injection of LiCl the activity of glutamic acid decarboxylase (GAD) was reduced by 29% in the striatum (2 meq/kg LiCl) and by 38% in the cerebral cortex (10 meq/kg LiCl). In contrast, striatal GAD was activated by 34% 1 h after the injection of 10 meq/kg of LiCl; this dose also reduced the endogenous striatal GABA level by 24%. After 14 days of oral LiCl administration (2 meq/kg/day): a) cortical GAD activity was enhanced by 50% and GABA concentration was decreased by 28%; b) no changes were observed in the striatum. These findings suggest that: LiCl administration stimulates GABA-ergic function in specific areas (depending on the dose and length of treatment) increasing both GAD activity and probably GABA release. This occurs in the striatum after acute treatment only with a high dose, and in the frontal cerebral cortex after chronic treatment with a low dose.

4-Aminobutyrate Transaminase↗
PubMed1986

Time-related response of central serotonergic function to lithium administration.

The possibility of "acute" (1 hr) changes in serotonergic function by lithium chloride (LiCl) administration was investigated in the rat corpus striatum and frontal cerebral cortex: an increase in 5-HT biosynthesis in vivo and 5-HIAA levels was observed in both areas. After chronic LiCl treatment (14 days) only cortical 5-HIAA levels were reduced. These changes were not correlated with plasma lithium levels. Consequently, LiCl "acutely" (1 hr) probably enhances striatal and cortical serotonergic transmission, this response varying with time of treatment as a result of possible neuronal compensatory mechanisms.

Animals↗
PubMed1985

Striatal dopamine and motor activity changes observed shortly after lithium administration.

Lithium chloride was given to rats i.p. at single doses of 2 and 10 meq/kg, respectively. It produced a suppression of motor activity and an increase in the dopamine content of the striatum. The magnitude of these effects were dose- and time-dependent as well as transient in nature. After 60 min of injection, the higher dose (10 meq/kg) reduced motor activity by 67% and increased striatal dopamine content by 56% while the lower dose (2 meq/kg) reduced motor activity by 42% and elevated striatal dopamine by 36%. These effects vanished 24 h after administration regardless the dose employed. None of the two doses of LiCl altered either dopamine biosynthesis in vivo (measured as the accumulation of a precursor of synthesis after decarboxylase inhibition), or the activity of tyrosine hydroxylase ex vivo under subsaturating conditions (i.e. enzyme activity in the tissues obtained from the animals post mortem). An increased deamination of tyramine by monoamineoxidase (MAO) was found in striatal homogenates after 60 min of the injection of 2 or 10 meq/kg of LiCl. This was due to a lower Km for the substrate as revealed by kinetic studies. LiCl treatment did not change the proportion of MAO A:B. As neither dopamine synthesis was increased nor the activity of the catabolic enzyme MAO was reduced (but it was oppositely enhanced), the increment in striatal dopamine content might have likely resulted from a reduced release and/or an increased amine reuptake by the neurons. We postulate that the reduced motor activity observed shortly after injection of LiCl would be related to an interference with striatal dopaminergic neurotransmission.

Animals↗
PubMed1985

Changes in GABAergic system parameters after chronic administration of bicuculline.

Male Wistar rats were chronically treated with 2 mg/kg per day bicuculline i.p. during 10 days. Biochemical parameters related to the GABAergic system in CNS were analyzed. A 63% increase in glutamic acid decarboxylase activity was found in treated animals. Endogenous GABA levels were not modified. The treatment increased Bmax of GABA binding by 112% without changing the KD value. The treatment decreased Bmax of diazepam binding by 40% whereas it did not change the KD value. Diazepam binding was enhanced by in vitro addition of GABA at the same extent as in treated animals.

Animals↗
PubMed1985

Effects of cocaine on several adrenergic system parameters.

The effect of acute and chronic administration of cocaine on the sympathetic nervous system in the cardiac tissue and the adrenal glands of rats were studied. Both with acute and chronic administration of the drug, the concentration-response curve to (-)-norepinephrine on the isolated rat atria was shifted to the right, with a lower pD2. The endogenous ventricular norepinephrine levels remain unchanged after acute injections of cocaine, but when the drug was administered chronically, the endogenous neurotransmitter content were augmented about 50%. The tyrosine hydroxylase activity in atria and adrenal homogenates decreased after chronic injections of cocaine, while it was not observed any modifications in the enzyme activity after acute administrations of the drug.

Adrenal Glands↗
PubMed1985

Benzodiazepine binding sites in rat submaxillary gland: absence of markers of GABA system.

Specific binding of [3H]diazepam to the nuclear, mitochondrial and microsomal subcellular fractions of the rat submaxillary gland is reported. Apparent KD values were similar in the three fractions studied (around 80 nM). The nuclear and mitochondrial fractions contain 95% of the total sites detected (20 pmoles/mg prot.). The sites exhibit a much higher affinity for Ro 5-4864 than for clonazepam or Ro 15-1788, and are not modified by 10(-6) to 10(-4) GABA or 10(-5) M bicuculline. Neither sympathetic denervation or parasympathetic decentralization modified [3H]Dz binding, which is found to be considerably lower in the early post-natal state as well as following duct ligation of the gland of adult rats. The results suggest that these peripheral Bz binding sites are mainly located in the acini. No specific GABA binding or GAD activity was detected either in the presence or absence of NaCl. Very low levels of endogenous GABA (58 +/- 3 nmoles/g tissue) were found in homogenates of the gland.

Animals↗
PubMed1985

Sexual differences in the effect of serotonin on LH secretion in rats.

The effect of 5-hydroxytryptophan (5-HTP), a serotonin (5-HT) precursor, on luteinizing hormone (LH) secretion was studied in prepubertal male and female rats of different ages. In females 5-HTP stimulated LH release on days 16, 18 and 20 but not in older rats (26, 30, 35 days of age). No effects of 5-HTP on LH levels were observed in males. The positive feed-back mechanism of oestrogen-progesterone (E-P), that normally matures in the female between 20 and 26 days, was inhibited by 5-HTP in all the ages studied during prepuberty (26, 30 and 35 days old). On the other hand, in adult ovariectomized rats, 5-HTP administration not only decreased the high LH levels induced by ovariectomy, but the LH release response to E-P as well. These results indicate that there are sexual differences in the effect of 5-HT on LH in prepubertal rats younger than 26 days old. Administration of p-chloroamphetamine (PCA) a serotonin neurotoxin selective for serotoninergic neurons that depletes 5-HT levels in the brain, induced a significant increase in the LH release response to LRH in females, but had no effect in males. These results, besides suggesting a probable pituitary participation in the 5-HT action on LH secretion in the female, appear to indicate the existence of sexual differences in the effect of 5-HT in adult rats.

5-Hydroxytryptophan↗
PubMed1984

Effect of triamterene on tyrosine hydroxylase activity.

Triamterene, which is structurally similar to the natural cofactor of tyrosine hydroxylase, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, inhibited tyrosine hydroxylase in rat adrenal gland homogenates and was found to be a competitive inhibitor of the synthetic cofactor 6,7-dimethyl-5,6,7,8-tetrahydrobiopterin. When triamterene (30 mg/kg i.p.) was administered to rats, a significant decrease in the adrenal, whole brain and kidney enzyme activities was observed after 90 min; if the drug was given orally, the diuretic affected only adrenal tyrosine hydroxylase. In both cases the drug decreased potassium excretion to 1/5 of control values and increased the excretion of sodium. Catecholamine levels in atria, kidneys, adrenal glands and whole brain were not affected in acute experiments. Chronic treatment (triamterene 30 mg/kg p.o. twice daily during 4 days) inhibited tyrosine hydroxylase and decreased catecholamine levels in the kidneys. Low potassium excretion was observed throughout the 4 days of treatment. In these chronic experiments the inhibition of the adrenal enzyme seen in acute treatments was not observed. This recovery cannot be explained by an increase in the adrenal biopterin levels. It could be mediated by an induction of the adrenal tyrosine hydroxylase.

Adrenal Glands↗
PubMed1984

Acute effects of lithium chloride on noradrenergic neurons from rat cerebral cortex.

Acute effects of lithium chloride upon the parameters of central noradrenergic function were assessed at either a therapeutic dose (2 m-equiv/kg) or a toxic one (10 m-equiv/kg) on rats. Lithium chloride lacked a direct effect on tyrosine hydroxylase (TH), monoamine oxidase (MAO), or catechol-O-methyltransferase (COMT) in concentrations up to 2 mM. A single i.p. injection of both studied doses inhibited MAO a hr later. Endogenous NA levels in frontal cerebral cortex were increased by a therapeutic dose and slightly increased by a toxic dose. Uptake of [3H]NA was increased in pretreated tissues at a therapeutic level but decreased by a toxic dose. The unmetabolized [3H]NA was always increased over controls.

Animals↗
PubMed1984

Metoclopramide increases the release of catecholamines from isolated human phaeochromocytomas.

Metoclopramide increased the release of catecholamines from isolated human phaeochromocytomas but not from isolated rat adrenal glands employed as control tissue. This selective effect of metoclopramide may have resulted from the high endogenous levels of catecholamines found in the tumours. It is suggested that the administration of drugs which can potentially produce the release of catecholamines should be very carefully controlled in patients with phaeochromocytoma.

Adrenal Glands↗
PubMed1984

Effects of exercise on several adrenergic system parameters.

Rats were exposed to acute (1 day) or chronic (3 or 7 days) swimming exercise 1 or 2 hours daily. Chronic swimming exercise produced a shift to the right in the (-)-noradrenaline dose-response curve on isolated atria and a lower pD2 when it was compared with the control value. This indicates a decrease in the cardiac-adrenergic sensitivity to the adrenergic neurotransmitter. The ventricular endogenous levels of noradrenaline were kept unchanged in the acutely and chronically exercised rats. The hydroxylation of tyrosine was augmented after acute swimming exercise in intact adrenal gland, and this could be related to the earlier regulatory mechanisms in the synthesis of the neurotransmitter. The increase observed in the hydroxylation of tyrosine in intact adrenal gland after chronic swimming exercise has been proposed to be related to an increase in the synthesis of the enzyme, since a similar elevation in the tyrosine hydroxylase activity was observed in tissue homogenates. On the other hand, while no activation of the enzyme was observed in atria after acute exercise, the chronic treatment only produced a clear increase in the homogenate tyrosine hydroxylase activity but not in the hydroxylation of tyrosine in intact atria. The monoamine oxidase activity was decreased in adrenal gland after acute swimming.

Animals↗
PubMed1984

The neurotoxic compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) depletes endogenous norepinephrine and enhances release of [3H]norepinephrine from rat cortical slices.

The alkylating compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) injected to rodents blocks norepinephrine (NE) uptake and reduces endogenous NE levels in the central nervous system and in the periphery. To investigate the processes leading to these alterations, rat cortical slices were incubated in the presence of DSP4. Cortical NE was depleted by 40% after incubation of slices in 10(-5) M DSP4 for 60 min and this was blocked by desipramine. The spontaneous outflow of radioactivity from cortical slices labeled previously with [3H]NE was enhanced markedly both during exposure to DSP4 and during the subsequent washings, suggesting that NE depletion could be due to this stimulation of NE release. The radioactivity released by DSP4 was accounted for mainly by NE and its deaminated metabolite 3,4-dihydroxyphenylglycol. The enhanced release, independent of external Ca++, apparently originated from the vesicular pool as it was absent after reserpine pretreatment. Activities of the enzymes related to NE synthesis were not altered by DSP4 in vitro and only monoamine oxidase activity was inhibited at high concentrations. Thus, the depletion of endogenous NE produced by DSP4 is probably due to a persistent enhancement of its release from the vesicular pool. Fixation of DSP4 to the NE transport system is necessary but not sufficient to produce the acute NE depletion and the characteristic long-term actions of the compound.

Amines↗
PubMed1984

Further studies on the histamine metabolism in the M-2 adenocarcinoma.

Further studies of the histamine metabolism in the M-2 adenocarcinoma have shown that the tumor and the intestinal histidine decarboxylase should have similar conformations, since both enzymes exhibit superimposable curves of activity vs. pH as well as nearly identical 50% inhibitory concentrations for the specific inhibitor NSD-1015. It has also be found that the increase of the radioactivity uptake by the tumor nuclear fraction compared to the intestinal nuclear fraction after their incubation with 3H-histamine, may be due to qualitative differences between the nuclei, since endogenous contents of DNA and associated proteins were not significantly different. The specific binding of 3H-histamine to different purified DNAs demonstrated very dissimilar proportions of bound histamine, suggesting a possible interaction of histamine with DNA, similar to some of the proposed mechanisms for the modulation of the genomic expression of DNA by some polyamines.

Adenocarcinoma↗