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Biomedical subjects

C Marin

Publications and source records attributed to C Marin.

At least 73 records · Page 4Linked to original sources

Dopamine D1 receptor stimulation but not dopamine D2 receptor stimulation attenuates haloperidol-induced behavioral supersensitivity and receptor up-regulation.

The effect of selective dopamine D1 and D2 receptor agonists on chronic haloperidol-treated rats was studied. Haloperidol treatment produced a 77% increase in apomorphine-induced sterotypy. The administration of the selective dopamine D1 receptor agonist SKF38393 alone or in combination with the selective dopamine D2 receptor agonist quinpirole attenuated the effect of haloperidol. Treatment with quinpirole alone did not have a significant effect on the response to haloperidol. Haloperidol did not modify the number of dopamine D1 receptors but increased that of dopamine D2 receptors. SKF38393 reversed the effect of haloperidol on dopamine D2 receptor binding. Co-administration of SKF38393 and quinpirole did not modify the increase in the number of dopamine D2 receptors induced by chronic treatment haloperidol. The results confirm a dissociation between behavioral supersensitivity and dopamine receptor up-regulation, suggesting that other mechanisms may be involved in the expression of behavioral supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

D1 and D2 dopamine receptor-mediated mechanisms and behavioral supersensitivity.

The contribution of D1 and D2 dopamine (DA) receptor mechanisms to the behavioral supersensitivity and receptor upregulation induced by chronic DA antagonist administration were compared. Rats received either the selective D1 DA receptor antagonist SCH23390, the selective D2 DA receptor antagonist raclopride, their combination, or haloperidol, a predominantly D2 antagonist, for 21 days. Equivalent cataleptogenic doses of all drugs and drug combinations were employed. Tolerance to the cataleptic response was observed only in the haloperidol-treated group. Apomorphine-induced stereotypies were significantly enhanced in SCH23390-, raclopride-, and haloperidol-treated rats. In contrast, coadministration of both SCH23390 and raclopride had no effect on apomorphine-induced stereotypy. These findings suggest that neuroleptics blocking in equal proportion D1 and D2 receptor sites might be less likely to induce tardive dyskinesia and drug tolerance than those acting selectively on one or the other of these receptor subtypes.

Animals↗

Ubiquitin in cerebral amyloid angiopathy.

Immunohistological findings in cerebral blood vessels of 4 cases with cerebral amyloid angiopathy (CAA) were compared with those of 4 Alzheimer's (AD) cases. A panel of antibodies against 2 neurofilament subunits (BF10 and RT97), a microtubule-associated protein (TAU) and ubiquitin were used. CAA cases showed a strong immunoreactivity for ubiquitin in blood vessel wall. Senile plaques (SPs) in CAA cases showed strong ubiquitin positivity but the central amyloid core was negative. AD brains showed immunoreactivity with all antibodies in SPs and neurofibrillary tangles (NFTs); blood vessels were consistently negative for ubiquitin. Control brains showed few SPs and NFTs; these were positive for ubiquitin, but blood vessels were negative. These results indicate that vascular amyloid deposition in CAA and AD may have different pathophysiological mechanisms.

Adenosine Triphosphate↗

Effect of Gi protein ADP-ribosylation induced by pertussis toxin on dopamine-mediated behaviors.

The effect of Gi protein modification produced by intrastriatal pertussis toxin injection on dopamine (DA)-mediated behaviors was studied. Administration of the selective D2 agonist quinpirole induced ipsilateral rotation but the selective D1 agonist SKF 38393 did not. However, SKF 38393 was able to increase the rotation induced by quinpirole. The selective D2 antagonist raclopride and the selective D1 antagonist SCH 23390 both blocked the effect of quinpirole. Striatal levels of cAMP were measured in both intact and pertussis toxin injected striatum. SKF 38393 induced a significant increase in cAMP, but quinpirole had no effect. When both drugs were administered together, quinpirole attenuated the SKF 38393-induced increase in cAMP levels. Moreover, quinpirole-induced attenuation of SKF 38393 effect was greater in intact striatum. In pertussis toxin-injected striatum, quinpirole only attenuated SKF 38393-induced increase of cAMP to control levels. This imbalance between intact and injected striatum might be the cause of the rotation in pertussis toxin-injected rats suggesting an important role for G proteins in DA receptor interactions.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Triggering of the proteinase dipeptidyl peptidase IV (CD26) amplifies human T lymphocyte proliferation.

CD26 (Ta1, dipeptidyl peptidase IV) is a Mr 105,000 protein expressed at high levels on activated T lymphocytes and is a potential marker of memory T cells. Reciprocal immunodepletion and solid phase double determinant binding studies showed that mAb AC7 and the CD26-specific mAb anti-Ta1 reacted with spatially distinct sites on the same molecule. The proteinase dipeptidyl peptidase IV (DPP IV) was immunoprecipitated with mAb AC7 and its enzymatic activity directly assayed using an enzyme overlay membrane system. High levels of DPP IV activity were detected on the T cell tumor line CCRF-HSB-2 and on PBMC stimulated by a variety of methods. By itself, soluble mAb AC7 was not mitogenic for T cells but enhanced T cell proliferation that resulted from treatment with phorbol myristic acetate (PMA) in the presence of accessory cells. T cell proliferation was also induced by co-immobilized mAb AC7 and mAb OKT3 (anti-CD3). Cultures of T cells growing in the presence of IL-2 responded with accelerated growth when exposed to a combination of immobilized mAb AC7 and soluble mAb OKT3, a result not seen with freshly isolated T cells.

Antibodies, Monoclonal↗

[The partner eye in unilateral malignant glaucoma].

The fellow eyes of 9 Patients suffering of unilateral classical malignant glaucoma have been throughly examined short after the onset of malignant glaucoma. In 3 cases they were apparently normal, in other 3 cases they exhibited an intermittent primary angle closure glaucoma and in the remaining 3 ones an absolute glaucoma. The therapeutic options of these fellow eyes are discussed.

Adult↗

Effect of chronic D-1 and/or D-2 dopamine antagonist treatment on SKF 38393-induced non-stereotyped grooming.

The effects of chronic D-1 and/or D-2 dopamine (DA) receptor blockade on a putative D-1 DA receptor-mediated behavioral function was studied in rats treated for 21 days with the selective D-1 antagonist SCH 23390, the predominantly D-2 antagonist haloperidol, or the combination of both drugs at the same daily doses. Four days after the last drug dose, the non-stereotyped grooming response to the selective D-1 agonist SKF 38393 increased in SCH 23390-pretreated rats decreased in haloperidol-pretreated rats compared to controls, but remained unchanged in animals receiving both drugs. Underlying DA receptor changes and the resulting imbalance between D-1 and D-2 receptor presumably contribute to these effects, suggesting that the upregulation of one DA receptor subtype may modify the expression of behaviors associated with the other subtype.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Dopamine D1 receptor modulation of pilocarpine-induced convulsions.

The contribution of dopaminergic mechanisms to the generalization of epileptic activity was studied in rats given pilocarpine after pretreatment with selective dopamine agonists. At the dose of 200 mg/kg, pilocarpine produced limbic stereotypes but not convulsions or seizure-related brain damage. Pilocarpine, 200 mg/kg, following pretreatment with the D1 agonist (RS)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine, but not its (S)-enantiomer, induced convulsive activity as revealed by behavioral, electroencephalographic alterations and widespread brain damage. These features were identical to those produced by a higher, convulsant dose of pilocarpine (400 mg/kg). On the other hand, pretreatment with the D2 agonist 4,4a,5,6,7,8,8a,9-octahydro-5-n-propyl-2H-pyrazolo-3,4-g-quinoline failed to induce convulsions. Furthermore, the D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-n-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine -7-ol prevented the convulsive activity induced by both 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3 benzazepine plus pilocarpine (200 mg/kg) and pilocarpine (400 mg/kg), given alone. However, neither dopamine agonists nor antagonists altered the limbic stereotypes induced by pilocarpine, suggesting a dopamine system involvement primarily in the mechanisms of epilepsy generalization. The results suggest that pharmacological manipulation of dopaminergic transmission may provide an alternative approach to therapy of secondarily generalized epilepsy.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Synergy between a selective D1 antagonist and a selective D2 antagonist in the induction of catalepsy.

The cataleptogenic effects of the selective D1 dopamine receptor antagonist, SCH 23390, and the selective D2 dopamine receptor antagonist, raclopride, when administered alone or in combination were studied in rats using the vertical grid and horizontal bar methods. In either model both agents, given alone, produced dose-dependent catalepsy. When administered together, there was a marked synergy between the two drugs. Thus, a low dose of SCH 23390 resulted in a 10-fold shift to the left of the raclopride dose-effect curve. When the same low dose of SCH 23390 was administered together with a subcataleptogenic dose of raclopride, marked catalepsy was produced. The finding of synergy between selective D1 and D2 dopamine antagonists in the induction of catalepsy suggests that mixed antagonists may possess greater antipsychotic activity than neuroleptics acting mainly on one receptor subtype.

Animals↗

D-1 dopamine agonist administration reduces the threshold for convulsions produced by pilocarpine.

Focal, limbic seizures were produced by systemically administered pilocarpine (200 mg/kg, i.p.); as previously described this dose produces limbic stereotypies but neither convulsions nor seizure-related brain damage. The pretreatment, 5 minutes prior pilocarpine, with the D-1 agonist SKF 38393 (-ED50 = 1 mg/kg; i.p.) induced convulsions similar to those produced by a higher, convulsant dose of pilocarpine. On the other hand, the pretreatment with the D-2 agonist LY 171555 failed to induce convulsions. The D-1 receptor antagonist SCH 23390 prevented the convulsions induced by SKF 38393 plus pilocarpine (200 mg/kg). This study indicates that D-1, but not D-2, receptor stimulation converts subconvulsant doses of pilocarpine into convulsant ones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Improvement in HPLC fractionation of thyroxine-containing thyroglobulin tryptic peptides by prior Accell ion-exchange column chromatography.

The isolation and purification of the peptides containing the hormonogenic tyrosyl residues in thyroglobulin is of great interest to the understanding of structure-function relationships in this iodoprotein. This is usually performed in reduced alkylated selectively hydrolyzed thyroglobulin by subsequent HPLC fractionation. However, the main difficulty encountered when trying to isolate these peptides is their disproportion with respect to the total number of possible peptides (14 vs a total of 508). Several HPLC runs with different mobile phases are necessary and each run is accompanied with significant losses of the peptides to be purified. In an attempt to improve the separation of the T4-containing peptides in thyroglobulin tryptic digests from the much more abundant iodotyrosine-containing ones, which are present as contaminants, we have used a very simple and fast step prior to the HPLC fractionation as it is a self-packed ion-exchange column chromatography. This preliminary step results in an improvement in the separation of these peptides and leads to a relative enrichment of the hormonogenic peptides falling in different zones of the HPLC chromatogram, which facilitates their subsequent separation and purification by HPLC.

Acetonitriles↗

Locomotor activity and stereotypy in rats following repeated apomorphine treatments at 1-, 3-, or 7-day intervals.

In two experiments, the effects of repeated intermittent administration of a relatively high dose of apomorphine (5 mg/kg) on locomotor activity and/or stereotypic behavior in rats was determined. In Experiment 1, male rats were given ten subcutaneous (SC) injections of apomorphine or vehicle and tested for locomotor activity and stereotypy. The first nine injection test sessions were given at 3-day intervals and the tenth injection test session was given 18 days following the ninth session. In Experiment 2, male rats were tested for locomotor activity following ten SC injections of apomorphine or vehicle with either a one- or seven-day interval between injections. Major findings were as follows: a) apomorphine produced progressively greater increases in locomotor activity with each succeeding injection (i.e., sensitization); b) sensitization to the locomotor activity stimulating effects of apomorphine developed with interinjection intervals of one, three, and seven days; c) the sensitization effect was maintained over the 18-day drug-free break; and d) the effect of apomorphine on stereotypic behavior did not significantly change with repeated injections. These findings indicate that even a single dose of apomorphine induces relatively long-lasting neurobiological changes. Moreover, these findings are consistent with the view that separate neural pathways mediate locomotor activity and stereotypy in rats.

Age Factors↗