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R de Miguel

Publications and source records attributed to R de Miguel.

12 recordsLinked to original sources
PubMed1992

Early changes in the development of dopaminergic neurotransmission after maternal exposure to cannabinoids.

Perinatal exposure to cannabinoid derivatives has been shown to affect brain development. In this work, we studied the changes induced by maternal exposure to cannabinoids during gestation and lactation on the dopaminergic activity in the prosencephalic area of offspring of several days of development. This brain area contains an increasing population of dopaminergic terminals from the different dopaminergic pathways that become differentiated in the adult rat. We measured the endogenous content of dopamine and its intraneuronal metabolite, L-3,4-dihydroxyphenylacetic acid, and the activity of tyrosine hydroxylase as indices of dopaminergic activity. Results showed that perinatal exposure to cannabinoids caused several changes in the evolution of the dopaminergic indices studied. These changes were mainly observed in males. The only alteration in females occurred on the tenth day of development: An increase in dopamine content was observed with no changes in either the content of L-3,4-dihydroxyphenylacetic acid or tyrosine hydroxylase activity. In males, the content of both dopamine and L-3,4-dihydroxyphenylacetic acid were decreased on the day previous to birth in the animals exposed to cannabinoids. Although the reduction in its metabolite disappeared on the fifth day, the decrease in dopamine was maintained and it was correlated with a decrease in tyrosine hydroxylase activity. However, this decrease in the activity of tyrosine hydroxylase was followed by an increase on the tenth day. These results allow us to conclude that perinatal exposure to cannabinoids produces changes in the normal development of several indices of the activity of dopaminergic neurons in the brain area containing the most important population of dopaminergic endings. These changes were mainly observed in males. They could be responsible for a long-term alteration in the neurological processes in which these neurons are involved in the adult.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Time-dependent effects of ovarian steroids on tyrosine hydroxylase activity in the limbic forebrain of female rats.

In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats.

Animals↗
PubMed1991

Nigrostriatal and mesolimbic dopaminergic activities were modified throughout the ovarian cycle of female rats.

In this work, we have studied the changes in the functional state of nigrostriatal (NSDA) and mesolimbic (MLDA) dopaminergic neurons during the estrous cycle of the female rat. The activity of tyrosine hydroxylase (TH), the turnover rate (Kt) after inhibition of dopamine (DA) synthesis and the ratio between the contents of this amine and its metabolite, L-3,4 dihydroxyphenylacetic acid (DOPAC), were used as indices of neuronal activity. The neuronal activity of NSDA neurons rose during estrous and declined during proestrous, as reflected by the values of Kt and DOPAC/DA ratio measured during both phases. Interestingly, the course of variations in striatal TH activity was similar, although retarded in relation to the changes in neuronal activity. Thus, TH activity was high during diestrous, whereas it was low during estrous. The activity of MLDA neurons was reduced during proestrous. This can be concluded from the decreased Kt and DOPAC/DA ratio measured in this phase and it was accompanied by a low TH activity. Thereupon, both Kt and TH activity increased during estrous. These results indicate the existence of physiological changes in the functional state of both dopaminergic systems during the ovarian cycle, which are partially different for each neuronal pathway. This supports the existence of a specific regulation, and not indiscriminate effects, by the hormones involved in this cycle, mainly estradiol and progesterone.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Is prolactin playing a role in the regulation of catecholamine synthesis and release from male rat adrenal medulla?

Previous evidence allows one to suspect that prolactin (PRL) may be a physiological regulator of catecholamine (CA) synthesis and release in the adrenal gland of rodents. To explore this possibility, we studied the in vivo and in vitro metabolism and release of noradrenaline (NA) and adrenaline (A) in the adrenal gland of male rats. The study was carried out with animals exhibiting a moderate increase in plasma PRL levels induced by grafting of additional pituitaries or a severe hyperprolactinemia produced by diethylstilbestrol (DES)-induced pituitary hyperplasia. The latter animals exhibited a significant increase in adrenal weight, associated with decrease in tyrosine hydroxylase (TH) activity and in NA content. Moreover, the adrenal activity of phenylethanolamine-N-methyl transferease (PNMT) was decreased in DES-treated animals. Pituitary-grafted rats also displayed an increased adrenal weight, together with decreases in the activities of PNMT, catechol-O-methyl transferase and monoamine oxidase. These in vivo observations were followed by in vitro studies, which showed a decrease in the basal release of both CAs from incubated adrenals of DES-treated rats, with no changes in pituitary-grafted rats. In addition, exposure to PRL of the incubated adrenals of animals exhibiting normal PRL levels produced decreases in A release and storage and in TH activity. These observations allow us to conclude that: i) PRL appears to exert an inhibitory influence on the catecholaminergic activity in the adrenal gland; and ii) its effect seems to be exerted by a direct action on this gland.

Adrenal Medulla↗
PubMed1991

Lack of effect of prolactin on the dopaminergic receptor sensitivity in striatal and limbic areas after experimentally-induced alterations in its peripheral levels.

Although it had been suggested that prolactin (PRL) modulates the dopaminergic receptor sensitivity in extrahypothalamic areas, recent studies have questioned this role. We studied the effects of PRL on the receptor sensitivity in the striatum and the limbic forebrain, analyzing the number of D1 and D2 receptors and the amount of their second messenger, cyclic-adenosine monophosphate (cAMP). Tyrosine hydroxylase (TH) activity and dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) content were also measured as indices of presynaptic activity. The study was carried out in male rats submitted to either acute (PRL injection) or chronic (pituitary grafts or diethylstilbestrol (DES)-induced pituitary tumors) rises of plasma PRL levels. The results showed a common lack of effect of PRL on the dopaminergic receptor sensitivity in both brain areas and, only some few effects on presynaptic activity in the striatum. Thus, grafted rats showed a slight decrease in DA content in the striatum, but neither D1 and D2 receptor number and cAMP content nor DOPAC content and TH activity, were modified, whereas DES animals exhibited no changes in all the parameters studied. A single injection of ovine PRL caused a decrease in DOPAC content and an increase in TH activity in the striatum. In the case of the limbic area, both chronic and acute hyperprolactinemia failed to alter any of the indices studied. In summary, we cannot support the view that PRL plays a role as modulator of dopaminergic receptor sensitivity. The only effects were always produced at the presynaptic level on the striatum, and after acute treatment, which supports the possible development of tolerance after chronic changes in peripheral PRL levels.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Prolactin inhibits the activity of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells in a dose-dependent manner.

Prolactin can modulate the adrenal medulla function, but it has not yet been established whether its action is directly exerted on the adrenal medulla cells. In this work, we have studied the effect of several concentrations of prolactin on the synthesis, storage and release of norepinephrine and epinephrine using cultured bovine adrenal chromaffin cells. In these cells, prolactin inhibited the activity of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis, in a dose-dependent manner, from a concentration above 50 ng/ml of prolactin in the incubation medium. Surprisingly, this dose-dependent decrease was not accompanied by changes in the catecholamine release, since the secretion of both norepinephrine and epinephrine as well as the total catecholamine secretion were not significantly altered by the different prolactin concentrations. Moreover, the cellular content of both catecholamines was not altered by prolactin. In summary, these observations allow us to conclude that prolactin exerts a direct inhibitory effect on the tyrosine hydroxylase activity in cultured adrenal chromaffin cells without altering catecholamine release.

Adrenal Glands↗
PubMed1990

Time-course of the effects of ovarian steroids on the activity of limbic and striatal dopaminergic neurons in female rat brain.

This paper studies the time-course of the effects of pharmacological administrations of ovarian steroids on the functional state of dopaminergic terminals in the striatum and the limbic forebrain, using the ratio between the contents of dopamine (DA) and its metabolite, L-3,4 dihydroxyphenylacetic acid (DOPAC), as an index of nerve activity. Estradiol produced an increase in the dopaminergic activity of both limbic and striatal neurons, reflected in the high DOPAC/DA ratio observed in both areas. This estrogenic effect was only observed at 4 hours, disappearing in the subsequent times studied. The effect was antagonized by progesterone in both tissues, since a single injection of this steroid to estrogen-pretreated rats restored to control values the estradiol-induced increase, suggesting the existence of negative interactions between both steroids. Furthermore, treatment with progesterone produced also a late decrease of the DOPAC/DA ratio in the striatum, which was observed only in the animals nonpretreated with estrogens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Role of ovarian steroids on the catecholamine synthesis and release in female rat adrenal: in vivo and in vitro studies.

In a previous report, we describe the existence of an effect of ovarian steroids on the adrenal medulla activities of the enzymes involved in catecholamine (CA) catabolism. To complete that study, we have now examined the adrenal medulla activity of tyrosine hydroxylase (TH), the rate limiting enzyme of the CA synthesis, as well as the in vitro release of CAs from incubated adrenal medullas. The study has been performed with adrenal medullas from female rats with physiological (estrous cycle) or pharmacological (steroid treatment) alterations in their circulating levels of estrogens and progesterone. The in vitro release of CAs from incubated adrenal medullas of estradiol-treated rats was lower than that obtained in vehicle-treated animals. In consequence, the preovulatory increase of estradiol would be the responsible of the low in vitro release of CAs observed during the estrous phase of ovarian cycle. However, this steroid does not seem to affect the CA synthesis, since the adrenal medulla activity of TH was not altered after the estradiol treatment nor during the estrous cycle. On the contrary, progesterone treatment increased TH activity 24 h after the steroid injection. This effect was independent of estradiol. However, an estrogen-dependent increase in TH activity occurred short-time after the steroid administration. Although progesterone by itself failed to modify the in vitro release of both CAs, it was able to reverse the estradiol-induced decrease in epinephrine release. In summary, estradiol seems to decrease the ability of the adrenal medulla to release CAs to the peripheral blood, without affecting the CA synthesis, whereas progesterone mostly affects TH activity, being its effects temporary and partially depending on estrogens.

Adrenal Medulla↗
PubMed1989

[Activity of creatine kinase and its isoenzymes in hemolytic uremic syndrome].

Serum creatine kinase (CK) and CK isoenzymes (CK-MM, CK-MB and CK-BB) were measured in 35 healthy and 25 children with hemolytic uremic syndrome (HUS) at 48 h, 7 and 15 days after admittance. Total serum CK activity was measured with a commercially available kit ("CK-NAC", by Merck, cat 14327) and CK isoenzymes using the Helena laboratories method. The interassay coefficients of variation with these methods are the following: for the total CK activity, 10.95 and 9.15% for an enzyme activity of 42 and 142 U/L respectively; for the activity of the isoenzymes, 6.8, 8.0 and 15.1% for activities of 102, 67 and 30 U/L. Total CK activity at 48 h in HUS patients defined two groups, group 1 (G1) which is not different from the control group (CG) and group 2 (G2) which had a significantly higher activity, p less than 0.0005. The increase in total CK remained significant until the first week. Increase in total CK resulted from the increase in CK isoenzymes: CK-MM, CK-MB and CK-BB. Highly significant correlation coefficients (p less than 0.0005) were obtained between total CK and their isoenzymes. When we examined both groups of patients in relation to clinical parameters, no difference could be found although G2 showed higher urea and fibrinogen degradation products with significantly decreased platelet counts. Although the reasons for enzyme release are not understood, anoxia and chemical toxins have been incriminates.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1988

Effects of acute sodium omission on insulin release, ionic flux and membrane potential in mouse pancreatic B-cells.

The effects of acute omission of extracellular Na+ on pancreatic B-cell function were studied in mouse islets, using choline and lithium salts as impermeant and permeant substitutes, respectively. In the absence of glucose, choline substitution for Na+ hyperpolarized the B-cell membrane, inhibited 86Rb+ and 45Ca2+ efflux, but did not affect insulin release. In contrast, Li+ substitution for Na+ depolarized the B-cell membrane and caused a Ca2+-independent, transient acceleration of 45Ca2+ efflux and insulin release. Na+ replacement by choline in the presence of 10 mM glucose and 2.5 mM Ca2+ again rapidly hyperpolarized the B-cell membrane. This hyperpolarization was then followed by a phase of depolarization with continuous spike activity, before long slow waves of the membrane potential resumed. Under these conditions, 86Rb+ efflux first decreased before accelerating, concomitantly with marked and parallel increases in 45Ca2+ efflux and insulin release. In the absence of Ca2+, 45Ca2+ and 86Rb+ efflux were inhibited and insulin release was unaffected by choline substitution for Na+. Na+ replacement by Li+ in the presence of 10 mM glucose rapidly depolarized the B-cell membrane, caused an intense continuous spike activity, and accelerated 45Ca2+ efflux, 86Rb+ efflux and insulin release. In the absence of extracellular Ca2+, Li+ still caused a rapid but transient increase in 45Ca2+ and 86Rb+ efflux and in insulin release. Although not indispensable for insulin release, Na+ plays an important regulatory role in stimulus-secretion coupling by modulating, among others, membrane potential and ionic fluxes in B-cells.

Animals↗
PubMed1985

Nutrient insulin secretagogues decrease 45Ca2+ efflux from islet cells by a mechanism other than the inhibition of the Na+-Ca2+ countertransport.

The mechanism whereby nutrient insulin secretagogues decrease 45Ca2+ efflux from islet cells is controversial. It was studied with mouse islets perifused with Ca2+-free solutions. In the presence of Na+, glucose and ketoisocaproate inhibited 45Ca2+ efflux by about 50%. Substitution of choline+ salts for Na+ salts decreased the efflux rate by 45%, but did not prevent glucose from decreasing it further. Ketoisocaproate also inhibited 45Ca2+ efflux, but less markedly than in an Na+ medium. Omission of Na+ decreased the efflux rate even when it was already lowered by glucose or ketoisocaproate. It is thus clear that nutrient insulin secretagogues decrease 45Ca2+ efflux from islet cells by a mechanism other than the inhibition of the Na+-Ca2+ countertransport, possibly by increasing sequestration of the ion in cellular organelles.

Animals↗