PubMed Health⌕ Search

Biomedical subjects

A Pletscher

Publications and source records attributed to A Pletscher.

At least 55 records · Page 3Linked to original sources
PubMed1982

Rheo-optical shape analysis of human blood platelets.

Alterations in rheo-optical signals obtained from suspensions of human blood platelets treated in various ways (drugs, storage in the cold, stirring, etc.) were monitored. A self-normalizing instrument measuring scattered light and relative amplitude of rapid oscillation of light intensity (noise level) at different angles was used. The following results have been obtained: 1. The light scattered at an angle of 40 degrees was decreased with considerable selectivity by pseudopod formation, if aggregation was inhibited. 2. The noise levels at 0 degree and 40 degrees were selectively diminished by the transition from the discoid to the spheroid shape of the platelets. 3. At 40 degrees but not at 0 degree, the noise level responded without delay and was not influenced by aggregate formation. Using this method alterations in platelet form, i.e. spheroid transformation and pseudopod formation, can be specifically and continuously monitored. In addition, the noise level at 40 degrees is a definite quantitative measure of the discoid state. This allows the determination of platelet activation without manipulations such as changes in stirring rates or addition of drugs.

Adenosine Diphosphate↗
PubMed1982

Drug-induced release of biogenic amines from synaptosomes and blood platelets of guinea-pigs.

Synaptosomes from guinea-pig brain were compared with blood platelets (partly from previous experiments) regarding the action of imipramine, the benzoquinolizine derivative Ro 4-1284, tyramine and p-chlormethamphetamine (PCMA) on the contents of stored radio-labelled 5-hydroxytryptamine (5HT), dopamine (DA) and noradrenaline (NA). Normal and reserpinized preparations were used in order to differentiate between granular and extragranular (reserpine-resistant) sites. Imipramine, in concentrations greater than those inhibiting 5HT- and NA-uptake released the three amines from granular and extragranular sites and showed the same order of potency in synaptosomes as in platelets. The drug Ro 4-1284 acted on the granular amines only, but its action on NA was less potent in synaptosomes than in platelets. Tyramine and PCMA also caused an exclusive release of granular amines in synaptosomes, whereas in platelets the drugs released extragranular 5HT (and DA) as well as the granular amines. Tyramine was more potent in synaptosomes than in platelets, and PCMA showed a preferential effect on 5HT in synaptosomes but not in platelets. It is concluded that, regarding the action of monoamine-releasing drugs, platelets are only partial models for synaptosomes. However, they may be superior to synaptosomes in predicting the pattern of amine release in brain in vivo as seen with Ro 4-1284.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1982

Storage of biogenic amines in intact blood platelets of man. Dependence on a proton gradient.

The actions of ionophores with different ion specificities and of thrombin on the release of 14C-labeled 5-hydroxytryptamine, [3H]noradrenaline, and endogenous ATP were measured in human platelets suspended in media with various K+ and Na+ concentrations. Besides thrombin, those ionophores [monensin, nigericin, and the combination of carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) with nonactin and/or valinomycin] which cause a rapid collapse of H+ gradients induced a fast and virtually total release of 14C-labeled 5-hydroxytryptamine and [3H]noradrenaline into the various media. FCCP alone, which causes an inversion of the membrane potential to inside negative values, induced a considerably slower amine release. Changes in the K+ and Na+ gradients did not lead to amine release, nor did interference with energy transduction by antimycin A with or without glycolysis inhibitors. Monensin and FCCP did not release ATP, whereas thrombin, added before or after incubation of platelets with FCCP and monensin, caused a marked liberation of the nucleotide. It is concluded that in intact human platelets (a) the intragranular storage of 5-hydroxytryptamine and noradrenaline mainly depends on the proton gradient across the granular membrane, and (b) ionophores causing a collapse of H+ gradients induce non-exocytotic release of 5-hydroxytryptamine and noradrenaline from intracellular storage granules.

Anti-Bacterial Agents↗
PubMed1982

A new antagonist of the 5-hydroxytryptamine receptor of blood platelets.

The newly synthesized 1-desoxyfructo-alpha,beta-dehydro-4, 5-dioxotryptamine (M4) inhibited the 5-hydroxytryptamine (5-HT)-induced shape-change reaction of human and rabbit platelets and to a lesser extent the adenosine-3',5'-diphosphate-induced shape-change reaction of rabbit platelets. The 5-HT-antagonism was shown to be of the competitive type in human platelets. In the latter M4 also counteracted the 5-HT-uptake, but was virtually ineffective in releasing 5-HT. Another new derivative of desoxyfructo-5-HT (M5) was a 5-HT-agonist. It is concluded that M4 represents a new class of antagonists of 5-HT-receptors in platelets.

Blood Platelets↗
PubMed1981

Liberation of catecholamines and 5-hydroxytryptamine from human blood-platelets.

Spontaneous and drug-induced liberation of 14C-5-hydroxytryptamine (14C-5HT), 3H-dopamine (3H-DA) and 3H-noradrenaline (3H-NA) from normal and reserpinized human blood-platelets has been determined from measurements of the amine contents before and after incubation in tris-buffer. In normal platelets the spontaneous liberation of 3H-catecholamines was more marked than that of 14C-5HT, but was less in percent for all these labelled amines than in reserpinized platelets. Thrombin lowered amine contents more in normal than in reserpinized platelets. The initial thrombin-induced decrease of 14C-5HT, in contrast to that of 3H-catecholamines, showed a partial recovery after 30 min which was abolished by imipramine. The benzoquinolizine Ro 4-1284 diminished all the amines in normal, but not in reserpinized platelets. In normal platelets tryamine affected 14C-5HT and 3H-DA about equally, whereas 3H-NA much less. Octopamine showed a similar pattern as tryamine, but was less potent. P-chlormethamphetamine (PCMA) and amphetamine decreased 3H-DA less markedly than 14C-5HT and 3H-NA not at all. In reserpinized platelets these arylalkylamines induced a decrease of 14C-5HT but not of 3H-catecholamines. It is concluded that (a) 3H-catecholamines like 14C-5HT are mainly localized in the granular pool of normal human platelets, (b) the pattern of action of a drug on intra- and extragranular amines depends not only on the nature of the drug and the amine to be liberated, but in comparison with previous results also on the species, (c) platelets are not completely satisfactory models for monoaminergic neurons, especially catecholaminergic ones regarding drug-induced amine liberation.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1981

Liberation of catecholamines from blood platelets.

1 Platelet-rich plasma (PRP) of guinea-pigs with or without reserpine was preincubated either with [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT) plus [(3)H]-dopamine or with [(14)C]-5-HT plus [(3)H]-noradrenaline ([(3)H]-NA). After isolation on two successive dextran gradients the double-labelled platelets were incubated in Tris-buffer in the presence or absence of various drugs. The decrease in radioactivity in the platelets was measured in order to determine the amount of the amine that had been liberated.2 Spontaneous liberation of the labelled amines was more marked in reserpine-treated platelets than in normal ones and somewhat more pronounced for the (3)H-catecholamines than for [(14)C]-5-HT.3 The reserpine-like benzoquinolizine, Ro 4-1284, caused liberation of all three labelled amines in normal but not in reserpine-treated platelets. More [(3)H]-dopamine was liberated than [(14)C]-5-HT and less [(3)H]-NA.4 The arylalkylamines, tyramine and p-chloromethamphetamine (PCMA), liberated all three labelled amines from normal platelets, and [(14)C]-5-HT and [(3)H]-dopamine, but not [(3)H]-NA from reserpine-treated ones. In normal platelets dopamine was reduced to a greater extent than [(14)C]-5-HT and [(3)H]-NA to a smaller extent, whereas in reserpine-treated platelets [(14)C]-5-HT was more markedly diminished than [(3)H]-dopamine.5 The 5-HT uptake inhibitor, imipramine, had little influence on the spontaneous and drug-induced liberation of [(14)C]-5-HT and [(3)H]-dopamine.6 It is concluded that (3)H-catecholamines like [(14)C]-5-HT are mostly localized in the granular pool of platelets; the three drugs tested liberate [(3)H]-dopamine [(3)H]-NA and [(14)C]-5-HT from the granular pool. Ro 4-1284 does not liberate (3)H-catecholamines and [(14)C]-5-HT from extragranular sites whereas tyramine and PCMA also act on the extragranular pool of [(3)H]-dopamine and [(14)C]-5-HT but not [(3)H]-NA.7 The liberation of catecholamines from platelets differs from that of 5-HT in several respects and platelets are only partly comparable to neurones as far as drug-induced liberation of biogenic amines is concerned.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1981

Shape changes induced by biologically active peptides and nerve growth factor in blood platelets of rabbits.

1 Nerve growth factor (NGF), substance P (SP) and thymopoietin all caused shape change reactions of rapid onset in rabbit platelets. NGF had the highest maximal effect, and SP the lowest EC50 (concentration causing half maximal shape change). The action of SP was reversible within 5 min, whereas that of NGF lasted for at least 1 h. A series of other peptides were inactive. 2 After preincubation of platelets with SP, a second application of SP no longer caused a shape change reaction, whereas the effect of NGF was not influenced. 3 An oxidized NGF-derivative without biological activity did not cause a shape change reaction, neither did epidermal growth factor. 4 Prostaglandin E1 (PGE1) and pretreatment of the platelets with 3% butanol, which counteract the shape changes caused by 5-hydroxytryptamine (5-HT) and adenosine 3',5'-diphosphate, also antagonized those induced by NGF and SP. Neither heparin nor methysergide, an antagonist of 5-HT-receptors, influenced the shape change induced by NGF or SP. The action of NGF was also antagonized by a specific antibody to NGF. 5 Thymopoietin, like the basic polypeptide polyornithine (mol. wt. 40,000) was not antagonized by PGE1 and butanol. Heparin, which counteracted the effect of polyornithine, did not influence that of thymopoietin. 6 In conclusion, different modes of action are involved in the shape change of blood platelets induced by polypeptides and proteins. SP and NGF may act by stimulating specific membrane receptors.

Animals↗
PubMed1981

Interaction of D-LSD with blood platelets of rabbits: shape change and specific binding.

In blood platelets of rabbits, the shape change-inducing effect of D-lysergic acid diethylamide (D-LSD) has been compared with the D-LSD-binding. D-LSD, but not L-LSD, caused a shape change reaction (EC50 1.3 x 10(-9) M) which was inhibited by various 5-HT antagonists (methergoline and neuroleptic drugs), butaclamol showing marked stereospecificity. Strong inhibitors of 5 HT uptake were only weak in counteracting the D-LSD-induced shape change. Furthermore, D-[3H]LSD bound to platelets at a single saturable, high affinity, stereoselective site [Kd = (31.1 +/- 3.3) x 10(-9) M; Bmax = 28.9 +/- 2.7 fmols per 10(8) platelets]. This binding was strongly antagonized by D-LSD and methergoline and less by the hallucinogenic drugs, psilocin, bufotenin and N'N'-dimethyltryptamine. L-LSD an 5 HT, inhibitors of 5 HT uptake and neuroleptics, especially spiroperidol and butaclamol, had only a weak antagonistic effect. The latter showed stereospecificity. It is concluded that 1) the shape change reaction caused by D-LSD in platelets is mediated by the specific 5 HT-receptor, 2) the sites mediating the D-LSD-induced shape change reaction are not identical with those responsible for D-[3H]LSD-binding and both these sites are different from the 5 HT-transport sites and 3) with respect to D-LSD-binding sites, platelets and neurons are not exactly identical.

Animals↗
PubMed1980

Blood platelets as models for neurons: uses and limitations.

Platelets show similarities with 5-hydroxytryptaminergic neurons with respect to (1) uptake kinetics of 5-hydroxytryptamine (5-HT) at the plasma membrane, (2) inhibitory effects of tricyclic antidepressants and neuroleptics on 5-HT uptake, (3) granular storage of 5-HT and possibly catecholamines, (4) action of drugs interfering with granular and possibly extragranular amine storage and (5) reaction of the 5-HT receptor at the plasma membrane to 5-HT agonists and antagonists. Dissimilarities include (1) the uptake of catecholamines at the plasma membrane, (2) the biosynthesis of biogenic amines (absent in platelets, present in neurons) and (3) the turnover of 5-HT (slow or absent in platelets, fast in neurons). Although the above mentioned similarities are not absolute, platelets may be considered as reasonable models for some functions of 5-hydroxytryptaminergic neurons e.g. 5-HT uptake at the plasma membrane, intracellular storage of monoamines and reactions of 5-HT receptors to drugs. In addition, the shape change reaction of platelets can probably be used to identify those basic proteins and polypeptides which cause neuronal depolarization. The significance of disturbances of the monoamine system of platelets in neuropsychiatric disorders including Parkinson's syndrome is not yet clear in all respects. Therefore, some of the current ideas about the validity of platelets as models for neurons will be briefly reviewed in this article.

Biogenic Amines↗
PubMed1980

Similar kinetic characteristics of 5-hydroxytryptamine binding in blood platelets and brain membranes of rats.

Blood platelets and brain membranes of SIV and Lewis rats both exhibited two saturable binding sites for 5-hydroxytryptamine (5-HT) in the concentration range 1-100 nM. The Kd values for the high-affinity sites were 4-6 nM and for the low-affinity sites 20-40 nM in both tissues of both rat strains. Blood platelets had 100-200 times more binding sites per mg protein (Bmax) than brain membranes. Thus, 5-HT receptors of platelets may be used as models for those of cerebral 5-HT-neurons.

Animals↗
PubMed1979

Shape change of blood platelets induced by myelin basic protein.

Myelin basic protein (MBP) isolated from bovine spinal cord caused a marked shape change reaction of human blood platelets which was not accompanied by the release reaction and not inhibited by methysergide and spiroperidol. Only those basic proteins, including MBP, which had previously shown to exert neuronal depolarisation also induced the shape change reactions. Therefore, these findings may extend the use of platelets as neuronal models.

Animals↗
PubMed1979

Shape change reaction of platelets in protein-free medium: ultramorphology.

Transmission and scanning electron microscopy indicate that rabbit platelets incubated in protein-poor medium retain their reactivity to shape change-inducing agents such as 5-hydroxytryptamine, adenosine-5'-diphosphate and chlorpromazine. Such platelets may be used as models for drug-membrane interactions, e.g. in neuronal cells.

Adenosine Diphosphate↗
PubMed1979

Effect of diazepam on cerebral 5-hydroxytryptamine synthesis.

In the brains of normal and reserpinized rats both diazepam and amino-oxyacetic acid (AOAA) decreased the 5-hydroxytryptophan (5HTP) accumulation induced by the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). In reserpinized animals, the action of diazepam was antagonized by picrotoxin and bicuculline in doses which did not themselves influence the NSD 1015-induced rise in 5HTP. In conclusion, diazepam probably depresses 5HT synthesis via GABAergic mechanisms and this effect is not dependent on a functionally intact monoaminergic synaptic transmission.

5-Hydroxytryptophan↗