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Biomedical subjects

R Raisman

Publications and source records attributed to R Raisman.

At least 37 records · Page 2Linked to original sources
PubMed1985

Adrenergic receptors in frontal cortex in human brain.

The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

Adrenergic alpha-Agonists↗
PubMed1985

Tryptamine, a substrate for the serotonin transporter in human platelets, modifies the dissociation kinetics of [3H]imipramine binding: possible allosteric interaction.

Tricyclic antidepressants and nontricyclic serotonin (5-hydroxytryptamine) uptake blockers monophasically inhibit [3H]imipramine binding in human platelets. Similarly, serotonin and tryptamine inhibit the binding of [3H]imipramine in the low micromolar range and with a pseudo-Hill coefficient near unity. Dissociation of the [3H]imipramine receptor complex in the presence of uptake inhibitors follows first-order kinetics with a half-life of approximately 60 min. Although serotonin and tryptamine do not decrease [3H]imipramine binding when added under equilibrium conditions, simultaneous addition of serotonin or tryptamine with serotonin uptake inhibitors decreases the rate of ligand-receptor dissociation in a concentration-dependent manner. These data suggest a common site of action for serotonin, which is the substrate of the transporter system, and of tryptamine, its nonhydroxylated analog. This hypothesis is supported by the identification of a high-affinity (Km = 0.55 microM), saturable, and temperature-dependent uptake of [3H]tryptamine in human platelets. Uptake of [3H]tryptamine was inhibited potently by imipramine and nontricyclic serotonin uptake inhibitors with a potency similar to that observed for [3H]serotonin uptake. These data support the hypothesis that in platelets, [3H]imipramine, tricyclic, and nontricyclic serotonin uptake inhibitors bind to a common recognition site that is associated with the serotonin transporter but that differs from the substrate recognition site of the carrier through which serotonin and tryptamine exert a heterotropic allosteric modulation on [3H]imipramine binding.

Allosteric Regulation↗
PubMed1984

Adrenergic receptors in Parkinson's disease.

Alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors were measured in the pre-frontal cortex of parkinsonian patients post-mortem. The number of beta 2 receptors was the same in control and parkinsonian subjects. alpha 1 and beta 1 receptors increased in number, particularly in demented parkinsonian patients, while alpha 2 receptors decreased. The affinity constants were unchanged. The modifications seem to be related to lesion of the noradrenergic pathway from the locus coeruleus to the cortex. The relationship between this lesion and the symptoms of dementia and depression in parkinsonian patients is discussed.

Clonidine↗
PubMed1984

Reduced Vmax of 3H-serotonin uptake but unchanged 3H-imipramine binding in the platelets of untreated hypertensive subjects.

The uptake of 3H-serotonin, endogenous serotonin content and 3H-imipramine binding were measured in platelets of subjects with essential hypertension and matched control volunteers. The uptake of 3H-serotonin and endogenous serotonin levels in platelets were significantly reduced while 3H-imipramine binding did not differ in the two experimental groups. These results provide further evidence that the uptake site for serotonin and the binding site for 3H-imipramine although associated, may be modified independently.

Biological Transport↗
PubMed1983

[3H]imipramine binding in subcellular fractions of rat cerebral cortex after chemical lesion of serotonergic neurons.

The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.

5,7-Dihydroxytryptamine↗
PubMed1983

Specific high affinity [3H]imipramine binding sites in rat lung are associated with a non-neuronal uptake site for serotonin.

[3H]Imipramine binds to rat lung membranes. The binding is saturable, of high affinity and sodium-dependent. Drug displacement studies indicate that the binding site in rat lung is similar to that already described in the brain cortex. Tricyclic antidepressants inhibited [3H]imipramine binding in the lung in the low nanomolar range and through a competitive interaction. Serotonin and non-tricyclic serotonin uptake blockers inhibited [3H]imipramine binding in lung in a complex manner. Our results support the view that [3H]imipramine binding and the serotonin recognition site of the transporter are related but not identical.

Animals↗
PubMed1983

3H-Rauwolscine binding in platelets from depressed patients and healthy volunteers.

3H-Rauwolscine binds specifically and with high affinity to alpha 2-adrenoceptors in human platelets. In a study comparing the binding of 3H-rauwolscine in platelets obtained from 26 control volunteers with 19 hospitalised, untreated, severely depressed patients, the mean maximal binding (Bmax) and mean dissociation constant (Kd) of 3H-rauwolscine binding were found to be identical in both groups. After 7-12 days, treatment with different tricyclic antidepressant drugs there was a significant improvement in the depressive symptoms but no change in the 3H-rauwolscine binding. After an average of 23 days treatment with tricyclic antidepressants, and when the Hamilton Depression Rating Scores had returned to normal, the Kd and Bmax of 3H-rauwolscine binding were still unchanged.

Adjustment Disorders↗
PubMed1982

Concomitant decrease in [3H]imipramine binding in cat brain and platelets after chronic treatment with imipramine.

Cats were treated chronically with imipramine (7.5 mg/kg i.p. twice daily for 20 days). Maximal [3H]dihydroalprenolol binding was reduced in the cerebral cortex of the treated animals whereas maximal [3H]spiroperidol binding to 5HT2-receptors was unchanged. Maximal [3H]imipramine binding was decreased to a similar extent in both hypothalamus and platelets of the same animals. This parallel decrease in [3H]imipramine binding in brain and platelets is discussed in relation to the lower [3H]imipramine binding found in platelets from untreated depressed patients as compared to those from control volunteers.

Animals↗
PubMed1982

[3H-Imipramine binding to human platelets. A peripheral index in depressive syndromes (author's transl)].

3H-imipramine shows specific, high-affinity binding to human platelet sites. The characteristics of these specific binding sites are very similar to those previously described in the rat brain. The inhibitory effects of 11 tricyclic antidepressants on 3H-imipramine binding to human platelets were investigated. There was a significant correlation between the inhibition observed and the average therapeutic doses of antidepressants, which suggests that the binding sites may be involved in the mode of action of these drugs. The number of binding sites (Bmax) for 3H-imipramine was compared in 39 controls and in 37 hospital patients with untreated severe depressive syndrome and was found to be significantly smaller in depressed patients, without any modification of the affinity constant Kd. The significance of these findings and their changes under treatment are discussed.

Adult↗
PubMed1982

High-affinity [3H]desipramine binding in the peripheral and central nervous system: a specific site associated with the neuronal uptake of noradrenaline.

The specific binding of [3H]desipramine to various brain regions and peripheral tissues of the rat was of high affinity, rapid and reversible. It was inhibited with high affinity only by tricyclic antidepressants and noradrenaline uptake blockers. There was a highly significant correlation between the potencies of a series of drugs for the inhibition of [3H]desipramine binding and for the inhibition of noradrenaline uptake. Substrates for the noradrenaline uptake system however inhibited the binding of [3H]desipramine only at very high concentrations. Postganglionic sympathetic denervation of the submaxillary gland and the heart both resulted in a pronounced decrease in [3H]desipramine binding sites, which paralleled the reduction in endogenous noradrenaline levels. High-affinity [3H]desipramine binding sites thus appear to be localised on noradrenergic nerve endings and are probably closely associated with the neuronal uptake system for noradrenaline.

Animals↗
PubMed1982

3H-imipramine binding and serotonin uptake in platelets from untreated depressed patients and control volunteers.

Human platelets possess specific high-affinity binding sites for 3H-imipramine which have similar characteristics to the sites previously described in human and animal brain. In a group of untreated depressed patients, the Bmax of 3H-imipramine binding and the Vmax of serotonin uptake in their platelets were found to be significantly lower than in a group of control volunteers. There was no significant difference in the Kd values for 3H-imipramine binding but the Km values of 3H-serotonin uptake were decreased in the depressed patients. When the measurements of 3H-imipramine binding and 3H-serotonin uptake were compared in the same individual, however, there was no correlation between the individual Bmax and Vmax values or the Kd and Km values. These results suggest that although the 3H-imipramine binding site and the mechanism for serotonin uptake are associated, they are not identical.

Adult↗
PubMed1982

High-affinity 3H-imipramine binding: a new biological marker in depression.

High-affinity binding of the tricyclic antidepressant drug, 3H-imipramine, has been demonstrated in the brain of various species including man. These specific binding sites have many of the characteristics to be expected for the specific site of action of a drug and appear to be associated with the neuronal uptake mechanism for serotonin. Chronic administration of tricyclic antidepressant drugs or the prolonged application of other antidepressant therapies, such as electroshock and sleep-deprivation, resulted in decreases in the density of 3H-imipramine binding sites. Apparently identical 3H-imipramine binding sites have been found in blood platelets from a variety of species including man. Clinical studies have shown that untreated severely depressed patients have a lower density of binding sites in their platelets than control volunteers. Longitudinal studies of these patients indicate that the density of 3H-imipramine binding sites tends not to change during treatment with tricyclic antidepressant drugs and the subsequent recovery from depression. 3H-imipramine binding in brain and platelets is proposed as a new biological marker in depression and as a useful research tool in biochemical and clinical pharmacological studies in affective disorders.

Binding Sites↗