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Biomedical subjects

M Da Prada

Publications and source records attributed to M Da Prada.

At least 145 records · Page 8Linked to original sources
PubMed1976

Uptake and liberation of mepacrine in blood platelets.

1. Isolated platelets of guinea pigs incubated in Tyrode showed a rapid accumulation of 14C-mepacrine which was less dependent on temperature than that of 14C-5-hydroxytryptamine (5HT). 2. The uptake of mepacrine was not inhibited by imipramine, cocaine, ouabain, KCN, NaF, and reserpine. 3. Various 5HT-liberating drugs, e.g. Ro 4-1284 (benzoquinolizine derivative with reserpine-like action), amphetamine, tyramine and imipramine did not markedly affect the 14C-mepacrine content of platelets previously loaded with this compound. 4. Thrombin and chlorpromazine caused a liberation of 14C-mepacrine from the platelts which was however, less pronounced than that of 14C-5HT. 5. From these and previous findings it is concluded that 14C-mepacrine accumulates in the 5HT storage organelles by a reserpine-insensitive mechanism not dependent on an active transport at the cytoplasmatic membrane level.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1976

Accumulation of 5-HT in non-terminal axons after p-chloro-N-methylamphetamine without degeneration of identified 5-HT nerve terminals.

The effect of a single injection of d,1-p-chloro-N-methylamphetamine (PCMA) on 5-hydroxytryptamine (5-HT)- containing neurons in rat brain was investigated using fluorescence histochemical, electron microscopic and biochemical methods. PCMA caused in a dose-dependent manner (from 4.3 mg/kg), an increase of formaldehyde-induced indoleamine (IA) fluorescence in swollen non-terminal axons during the first 6 days and, in contrast, a diminution of IA fluorescence in nerve terminal regions for up to 42 days after treatment. These changes did not appear to be the result of destruction of 5-HT nerve terminals since at all time intervals investigated (12 h to 42 days), the fine structure and frequency of supra-ependymal 5-HT nerve terminals were unaffected. Moreover, no degenerating nerve terminals were observed in the suprachiasmatic nucleus. A marked transient decrease of IA fluorescence on day 2 in the 5-HT cell bodies B3-B9 was not followed by obvious morphological changes up to 42 days after PCMA. Therefore, the reduced 5-HT content of brain up to 42 days after treatment seems not to be due to a destruction of 5-HT neurons. Moreover, the damage to non-terminal 5-HT axons, as indicated by the 5-HT accumulation, seems not to be severe, at least not to those axons projecting to the cerebral ventricles and suprachiasmatic nucleus, since no degeneration of 5-HT nerve terminals was observed at any of the times investigated.

Animals↗
PubMed1976

Subcellular localization of the heparin-neutralizing factor in blood platelets.

1. The distribution of the heparin-neutralizing factor (platelet factor 4, PF4) in subcellular organelles of blood platelets of rabbits and man was investigated. 2. In both species the organelles storing 5-hydroxytryptamine (5-HT storage organelles) contained only trivial amounts of PF4. 3. In contrast, the content of PF4 was highest in the subcellular fractions rich in alpha-granules. 4. In conclusion, PF4 is probably localized in the alpha-granules and therefore the platelets contain at least two types of organelles (5-HT organelles and alpha-granules) capable of releasing their contents in response to the same stimuli, such as exposure to collagen, thrombin, etc.

Animals↗
PubMed1975

Interference of inhibitors of dopamine-beta-hydroxylase with uptake of monoamines by chromaffin granular membranes.

Disulfiram and bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA 63) markedly inhibited the Mg2+/ATP-dependent uptake of various monoamines, e.g. dopamine (DA), by isolated membranes of bovine adrenal chromaffin granules. Both compounds affected DA-beta-hydroxylase (DBH) activity more markedly than the uptake of DA. Other inhibitors of DBH, e.g. fusaric acid and diethyldithiocarbaminate (DDC), did not interfere with DA uptake. Disulfiram and FLA 63, in contrast to fusaric acid and DDC, also caused a partial inhibition of Mg2+-dependent ATPase. It is concluded that the inhibition of monoamine uptake by disulfiram and FLA 63 is not related to their effect on DBH.

Adenosine Triphosphatases↗
PubMed1975

Discrimination of monoamine uptake by membranes of adrenal chromaffin granules.

1 The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis. 2 Adenosine-5'-triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (-)-noradrenaline (NA), 5-hydroxytryptamine (5-HT), (plus or minus)-adrenaline and (plus or minus)-octopamine was greater than that of tyramine, (plus or minus)-metaraminol, tryptamine, beta-phenylethylamine and histamine. 3 At the higher concentration levels of the amines in the medium the ATP-dependent accumulation of dopamine, NA, adrenaline and 5-HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained. 4 Octopamine and 5-HT competitively inhibited the ATP-dependent uptake of NA, 5 Decrease in the incubation temperature or the presence of N-ethylameimide greatly reduced the ATP-stimulated amine accumulation. Ouabain had no effect on uptake. 6 Reserpine virtually abolished the ATP-dependent uptake of dopamine, NA and 5-HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine. 7 The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5-HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP. 8 The ATP content of the medium progressively decreased during the incubation of granular membranes. 9 It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP-stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP-stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.

Adenosine Triphosphate↗
PubMed1975

Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.

Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.

Alkaline Phosphatase↗
PubMed1975

A comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine.

Drug-induced rotational behaviour was studied in two groups of rats with differing chemical lesion of the right medial forebrain bundle (MFB). 6-hydroxydopamine (6-OH-DA), 3.5 mug, injected in one group, induced a marked lowering of dopamine (DA) and noradrenaline (NA) in the right hemiforebrain. 5,6-Dihydroxytryptamine (5,6-HT), 10 mug, injected in a second group, produced a profound and long-lasting depletion of 5-hydroxytryptamine (5-HT) and DA, but not of NA. Rotational behaviour induced in both groups by DA receptor agonists (apomorphine, piribedil, L-DOPA, ergometrine, ergocornine, 2-bromo-alpha-ergocryptine, ergocristine, methylergometrine) and agents releasing DA (d-methamphetamine, methylphenidate) were qualitatively identical and quantitatively very similar, suggesting a minor role of 5-HT striatal terminals in these experimental conditions. LSD induced contralateral rotation by direct stimulation of the DA receptor, while L-5-hydroxy-tryptophan (L-5HTP) was inactive.

5,6-Dihydroxytryptamine↗