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E Costa

Publications and source records attributed to E Costa.

At least 577 records · Page 32Linked to original sources
PubMed1976

Correlation between analgesia and the decrease of acetylcholine turnover rate in cortex and hippocampus elicited by morphine, meperidine, viminol R2 and azidomorphine.

In rats, an ED50 for analgesia of morphine, meperidine, viminol R2 or azidomorphine decreases the turnover rate of acetylcholine (TRACh) in cortex and hippocampus. These four analgetics fail to change to TRACh in striatum when given in a dose range from ED30 for analgesia up to a cataleptic dose. Viminol S2, a nonanalgesic stereoisomer of vimonol R2, fails to decrease the TRACh in cortex and hippocampus. Naltrexone, an opiate antagonist, also fails to change the cortical and hippocampal TRACh but it antagonizes the decrease in cortical and hippocampal TRACh elicited by the four analgetics. Since the ED50 of these four analgetics fails to change the TRACh in striatum which contains a high density of opiate receptors and intrinsic cholinergic neurons, but decreases the TRACh in hippocampus and cortex which contain a low density of opiate receptors, it can be inferred that opiate receptors are not exclusively involved in the regulation of TRACh. However, the results suggest that certain cholinergic pathways participate in the mediation of analgesia.

Acetylcholine↗
PubMed1976

A neurobiological role for a protein activator of cyclic nucleotide phosphodiesterase.

This work supports the idea that PDEA is bound and stored in brain particulate fraction. The release of PDEA into cytosol where the activator-sensitive PDE is located, is the first event in the process of the regulation of cAMP metabolism and inactivation. PDEA is released by cAMP-dependent phosphorylation of the activator-binding sites. This process is Ca2+ independent and does not occur in the presence of cGMP and cGMP-dependent phosphorylation. The free, soluble PDEA activates the high Km PDE in the presence of micromolar concentrations of Ca2+. This protein decreases severalfold the Km for cAMP of the high Km activator-sensitive PDE. PDEA regulates cAMP metabolism when the concentration of cAMP is elevated by a transsynaptic activation of adenylate cyclase. The rate of synthesis and the release of PDEA might be a part of the process of receptor sub- and supersensitivity, which has been reported during denervation or as a result of chronic treatment with drugs.

Adenosine Triphosphate↗
PubMed1976

Cyclic AMP content and regulation of tyrosine-3-mono-oxygenase in rat striatum.

The unilateral transection of nigro striatal dopaminergic axons produced a short lasting (15-30 min) increase in the affinity of striatal tyrosine 3-mono-oxygenase (TH), for a synthetic pteridine cofactor (DMPH4). The kinetic changes of striatal TH were paralleled by an increase of striatal cAMP content. Apomorphine (10 mg/kg i.p.) failed to block the activation of TH by cerebral hemisection. Haloperidol (5 mg/kg i.p.) and reserpine (5 mg/kg i.p.) also elicited a sudden and similar change in striatal TH activity but this response occurred without an increase in the cAMP content and lasted for longer than 2 hrs. If the hemisection of nigrostriatal pathway was performed after haloperidol or reserpine injection the activation of TH produced by these two drugs was reversed rapidly (about 30 minutes). Pretreatment with haloperidol or reserpine prevented the increase of striatal cAMP following cerebral hemisection. Moreover, haloperidol injected 30 min after cerebral hemisection failed to change the TH kinetic properties in the striatum ipsilateral to the lesion but it changed striatal TH in the side contralateral to the lesion. These results suggest that the increase in the affinity of striatal TH for the pteridine cofactor elicited by cerebral hemisection is not related to a lack of stimulation of DA autoreceptors. Moreover these experiments provide an evidence that postsynaptic dopamine receptors play a role in the activation of striatal TH elicited by haloperidol.

Animals↗
PubMed1976

In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum.

We have measured acetylcholine (ACh) content and turnover rate (TRACh) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 mumol/kg) and haloperidol (10 mumol/kg) reverse the decrease in striatal TRACh elicited by apomorphine (11 mumol/kg) while each antipsychotic affects the steady state and the TRACh in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRACh; chozapine (15 and 30 mumol/kg) neither decreases the content of ACh nor changes the TRACh in striatum. Moreover, 60 or 90 mumol/kg of clozapine causes a 40% decrease in ACh content without affecting the TRACh. Clozapine, but not haloperidol, antagonizes the increase in ACh content and the decrease in TRACh elicited by arecoline (64 mumol/kg) and oxotremorine (9 mumol/kg) in striatum. Clozapine resembles trihexylphenidyl (14 mumol/kg) and benztropine (12 mumol/kg) because it decreases the ACh content of striatum without changing the TRACh. Moreover, clozapine and benztropine reverse the increase in striatal TRACh elicited by haloperidol. The increase in striatal TRACh elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.

Animals↗