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Biomedical subjects

J M Saavedra

Publications and source records attributed to J M Saavedra.

At least 37 records · Page 2Linked to original sources
PubMed1977

Distribution of serotonin and synthesizing enzymes in discrete areas of the brain.

With the use of sensitive radio-enzymatic microtechniques, serotonin and its synthesizing enzymes, tryptophan hydroxylase and L-amino acid decarboxylase, can be quantitatively detected in discrete regions of the rat brain. A microdissecting technique allows us to study their localization in specific brain areas and nuclei. Serotonin and its related enzymes are concentrated in the raphe nuclei. Relatively high serotonin concentrations are also present in areas and nuclei of the hypothalamus, limbic system, and brain stem, as well as in the circumventricular organs and the pituitary gland. The localization of its synthesizing enzymes in the same regions suggests that the formation of serotonin actually takes place in these areas. Catecholamines are also present in the raphe nuclei of the rat. Changes in catecholamine metabolism result in changes in serotonin levels in specific brain areas. These results suggest that serotonin may be involved in the regulation of a number of autonomic functions, and in neuroendocrine control mechanisms. The neuroanatomical and biochemical relations between the catecholaminergic and serotonergic system in the brain support the hypothesis of a physiological interaction of these two systems in specific, localized brain structures.

Animals↗
PubMed1976

Effect of surgical isolation of the hypothalamus on its neurotransmitter content.

The concentrations of norepinephrine, dopamine-beta-hydroxylase, dopamine, tyrosine hydroxylase, phenylethanolamine-N-methyltransferase, serotonin, tryptophan hydroxylase, histamine, glutamic acid decarboxylase, and choline acetyltransferase were determined in selected hypothalamic nuclei and in the median eminence after deafferentation of the medial basal hypothalamus. Norepinephrine and dopamine-beta-hydroxylase fell markedly while dopamine and tyrosine hydroxylase did not. Serotonin also decreased in all regions studied; histamine decreased in none. Choline acetyltransferase, phenylethanolamine-N-methyltransferase, and glutamic acid decarboxylase declined in some areas, but not in others.

Animals↗
PubMed1976

Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites.

The zona reticulata, the subdivision of the substantia nigra containing dendrites of the dopaminergic nigro-neostriatal neurons, contains dopamine-sensitive adenylate cyclase activity. This nigral dopamine receptor is similar to the striatal dopamine receptor. These and previous data suggest a physiological role (or roles) for dopamine in the substantia nigra.

Adenylyl Cyclases↗
PubMed1976

Tyrosine hydroxylase and dopamine-beta-hydroxylase: distribution in discrete areas of the rat limbic system.

Tyrosine hydroxylase and dopamine-beta-hydroxylase have been measured in 34 discrete areas and nuclei of the limbic system of the rat. Both enzymes showed an uneven distribution in this system. The ratio between tyrosine hydroxylase and dopamine-beta-hydroxylase activities showed a significant correlation when compared with the ratio of dopamine and norepinephrine concentrations for the areas studied. The results strongly suggest that dopaminergic terminals are present in discrete areas of the limbic cortex, and several septal and amygdaloid nuclei, and allow the precise localization of dopaminergic and noradrenergic areas in the limbic system.

Animals↗
PubMed1976

Adrenaline-forming enzyme in brainstem: elevation in genetic and experimental hypertension.

The adrenaline-forming enzyme (phenylethanolamine N-methyltransferase) was elevated in the A1 and A2 regions of the brainstem of 4-week-old spontaneously (genetic) hypertensive rats and in the A1 region of adult experimentally (deoxycorticosterone acetate and sodium chloride) hypertensive rats. The administration of a phenylethanolamine N-methyltransferase inhibitor to experimentally hypertensive animals caused a reduction of the elevated blood pressure to normal values. These results implicate adrenaline-containing neurons in the brainstem in the development of hypertension.

Blood Pressure↗
PubMed1976

Peripheral and central catecholaminergic neurons in genetic and experimental hypertension in rats.

1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)-salt hypertensive rats. 2. In young SHR (4 weeks) the plasma values of bpth noradrenaline and dopamine-beta-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different. 3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats. 4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA-salt hypertensive rats. 5. In the adrenal glands of adult DOCA-salt hypertensive rats tyrosine hydroxylase activity was increased. 6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats.

Adrenal Glands↗
PubMed1976

Effect of stress on serotonin concentration and tryptophan hydroxylase activity of brain nuclei.

The effects of a single stressful stimulus on serotonin (5-HT) concentration and of repeated stressful stimuli on tryptophan hydroxylase (THy) activity were measured in individual hypothalamic nuclei and other rat brain regions using specific sensitive radioisotopic enzymatic microassays. Two h after formalin injection, 5-HT levels were increased in the dorsal raphe (RDN). Acute immobilization stress, however, reduced the concentrations of 5-HT in several of the hypothalamic nuclei: the medium eminence (ME), lateral amygdaloid nucleus, hippocampus, cingulate cortex (CCX) and RDN. Five consecutive daily immobilization periods failed to alter THy activity in any region examined. These results suggest a rapid release of 5-HT both from the cells and the axon terminals in the central nervous system, and failure, even with repeated stresses, to elicit induction of increased levels of the biosynthetic enzyme regulating the synthesis of the neurotransmitter.

Animals↗
PubMed1976

Lack of effect of various endocrine manipulations on tryptophan hydroxylase activity of individual nuclei of the hypothalamus, limbic system, and midbrain of the rat.

The tryptophan hydroxylase activity of individual nuclei of the limbic system, hypothalamus, and midbrain was determined after various endocrine manipulations in an attempt to identify specific endocrine-responsive serotonergic structures in the rat brain. Following adrenalectomy, thyroidectomy, castration, or treatment with pharmacological doses of dexamethasone, testosterone, or thyroxine, no changes in tryptophan hydroxylase activity occurred in any of the areas of brain examined. Furthermore, in large sections of the hypothalamus and midbrain, total tryptophan hydroxylase activity was unaltered, and no changes in Km for substrate or co-factor were found after adrenalectomy. This study, therefore, has failed to detect any hormonally responsive tryptophan hydroxylase activity in the rat brain. These findings suggest that endocrine-induced alterations in serotonin turnover, if they occur, do so without measurable changes in the activity or kinetic properties of tryptophan hydroxylase.

Adrenal Glands↗
PubMed1976

Biochemical and histochemical studies of biogenic amines in spinal cord trauma.

Highly sensitive enzymatic assays, microdissection techniques, and histochemical methods were used to investigate the effects of blunt trauma on rabbit spinal cord serotonin, norepinephrine, and dopamine concentrations. Within 5 minutes after trauma, norepinephrine and serotonin in gray matter decreased considerably at the lesion center. In white matter, norepinephrine decreased or was unchanged, but at the lesion edges serotonin increased. No changes in dopamine concentration were detected. Substantial changes in monoamines do occur after spinal cord trauma and serotonin may play a role in injury development.

Animals↗
PubMed1976

Biosynthesis and metabolism of endogenous tyramine and its normal presence in sympathetic nerves.

By use of a sensitive and specific enzymatic isotopic method for the determination of tyramine, the small quantities of this amine which are present endogenously in rat tissues, including brain, heart, kidney and salivary gland, have been quantitated. The levels of tyramine in brain were increased to a similar extent by injecting animals with a monoamine oxidase inhibitor, pargyline, and a dopamine beta-hydroxylase inhibitor, FLA-63; in contrast, pretreatment of animals with alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, did not lead to an increase in tyramine levels in brain. Pretreatment of rats with 6-hydroxydopamine resulted in a marked diminution in the tyramine content of rat atria and salivary gland. Denervation of the salivary gland decreased the endogenous level of tyramine approximately 50% in denervated glands compared to undenervated glands. These results suggest that tyramine exists at least partly in sympathetic nerves in many tissues.

Animals↗
PubMed1976

Octopamine as a putative neurotransmitter.

Octopamine is a normally occurring amine in nervous tissues in many species of animals. In mammals, octopamine is formed from tyramine through beta-hydroxylation by DBH in the sympathetic nerves, and it is partially stored in nerve endings with a subcellular distribution similar to that of NE. It is capable of replacing NE in its storage sites, and it is released by sympathetic nerve stimulation. High concentrations are found in the crustacean central nerve cord. Specific octopamine-containing cells have been identified in Aplysia and other lower animals. On the basis of neurophysiological evidence, the existence of specific octopamine receptors in Aplysia has been postulated. In insects, octopamine produces specific biochemical responses such as increased synthesis of cyclic AMP and phosphorylase activation. The present evidence strongly suggests that octopamine may function as a neurotransmitter in lower animals. Although the physiological role of this amine has not been established in mammals, it appears likely that octopamine may function as a cotransmitter together with NE in the peripheral sympathetic nervous system.

Adenylyl Cyclases↗
PubMed1975

Quantitative localization of biogenic amines in the spinal cord.

Recently developed highly sensitive radiometric assays for biogenic amines have been combined with microdissection techniques to localize and quantify these amines in different structures, and at various levels of rabbit and rat spinal cords. Assays were performed for serotonin, norepinephrine, dopamine and epinephrine. It was generally found that the highest concentrations of those biogenic amines were found in the lateral and ventral horns, slightly lesser concentrations were found around the central canal, and still lower concentrations were found in the dorsal horns. Relatively low amine concentrations were found in the white matter. These biochemical measurements correlate well with localizations indicated by histofluorescence methods but provide precise quantification. Comparisons with previously available, less sensitive biochemical measurements are discussed.

Animals↗