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M Memo

Publications and source records attributed to M Memo.

At least 127 records · Page 7Linked to original sources
PubMed1982

Agonist-induced subsensitivity of adenylate cyclase coupled with a dopamine receptor in slices from rat corpus striatum.

Incubation, for 30 min, of striatal slices with 10 microM dopamine, 10 microM apomorphine, or 10 microM SKF 38393 decreased dopamine-stimulated adenylate cyclase activity by 50-60%. This loss in dopamine-stimulated enzyme activity appears to be mediated by a persistent occupancy of recognition sites of the D-1 receptor because: (i) at 10 microM, SKF 38393, a selective D-1 receptor agonist, facilitates desensitization and Ly 141865, a selective D-2 receptor agonist, fails to elicit desensitization of dopamine-dependent adenylate cyclase; and (ii) preincubation with dopamine in the presence of 1 microM haloperidol but not 1 microM sulpiride curtails the desensitization of dopamine-dependent adenylate cyclase. In dopamine-desensitized striatal slices of the Kd for N-propylnorapomorphine binding is increased but the content of membrane-bound calmodulin and the activation of adenylate cyclase by NaF and cholera toxin are decreased significantly. In striatal slices incubated with dopamine for prolonged time periods the coupling of the GTP-binding protein with adenylate cyclase and dopamine recognition sites may be impaired and the content of membrane-bound calmodulin is decreased.

Adenylyl Cyclases↗
PubMed1981

Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain areas.

There is now evidence that two classes of dopaminergic receptors are present in CNS of the rat: D1, associated, and D2, not associated with adenylate cyclase activity. Drugs which interact specifically with D2 receptor are more capable of antagonizing the hyperkinetic behavior induced by lead exposure in rat. They also have a beneficial effect in children with hyperkinetic disorders. We found that the dose (-)sulpiride which causes sedation is lower in lead intoxicated animals than in controls. On the contrary, haloperidol produces sedation with the same potency in lead-treated and in control rats. The reported behavioral effects were found to be correlated with biochemical changes. In fact, in lead exposed rats D2 receptors, measured by (-)-[3H]sulpiride stereospecific binding, are altered, while D1 receptors seem not to be affected. The alterations are different according to the area examined: D2 receptor function is increased in the striatum and decreased in the nucleus accumbens. The impairment of D2 receptor might explain the better capacity of substituted benzamides to improve the hyperkinetic behavior observed in lead exposed rats.

Adenylyl Cyclases↗
PubMed1981

Identification of beta-adrenergic receptor binding sites in rat brain microvessels, using [125I]iodohydroxybenzylpindolol.

Brain microvessels were prepared from rat cerebral cortex. The purity was confirmed by phase-contrast microscopy and by the measurement of an enzymatic marker, gamma-glutamyltranspeptidase. The microvessel preparation was subjected to radioreceptor assay using a 125I-labelled beta-adrenergic antagonist, hydroxybenzylpindolol (IHYP). The binding was linear with protein concentration up to at least 80% microgram per tube. It was saturated at 200 pM IHYP concentration. The KD value calculated by Scatchard analysis was 69.4 +/- 9.9 pM. The maximum binding (Bmax) was 107 +/- 4 fmol/mg protein. The binding reached equilibrium within 30 min and was dissociated by addition of (-)-propranolol. The inhibitory effects of isomers of propranolol and isoproterenol on this binding showed that (-)-isomers were two orders of magnitude more potent than the (+)-isomers. Other neurotransmitters did not affect IHYP binding. The characteristics of the binding, saturability, high affinity, reversibility and stereospecificity, suggest tha IHYP is bound to beta-adrenergic receptor sites located on brain microvessels.

Animals↗
PubMed1981

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics.

It is now generally recognized that dopamine receptors exist in the CNS as different subtypes: D1 receptors, associated with adenylyl cyclase activity, and D2 receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D1 and D2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D1 receptors, and sulpiride, a selective antagonist to D2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D2 receptors. In fact under these conditions 3H-(-)-sulpiride binding, which is a marker of D2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride itself produces supersensitivity of D2 receptors. Moreover, sulpiride does not induce supersensitivity of the D1 receptors, characterized by 3H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral lesion of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3H-spiroperidol and 3H-(-)-sulpiride binding. These findings suggest that D1 and D2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

Adenylyl Cyclases↗
PubMed1980

Aging process affects a single class of dopamine receptors.

[3H]Spiroperidol and [3H](-)-sulpiride specific binding have been used to assay for D1 and D2 dopaminergic recognition sites in striatal membranes of aged rats. While [3H]spiroperidol binding shows a decreased number of binding sites, no changes have been detected in [3H](-)-sulpiride binding, which is a marker for D2 dopaminergic receptors. Data obtained with GTP and DA-dependent adenylyl cyclase activity confirm the hypothesis that aging selectively affects in rats those dopaminergic receptors coupled to the formation of cyclic AMP (D1).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Impairment of brain neurotransmitter receptors in aged rats.

Dopamine and gamma-aminobutyric acid (GABA) receptor functions have been measured in various brain areas of aged rats. [3H] Spiroperidol binding is decreased in various dopaminergic brain areas, particularly in striatum and tuberculum olfactorium. In striatum the number of binding sites for [3H] spiroperidol is similar in both groups of animals, while the affinity is reduced in senescent rats. Moreover, in the pituitary a 50% increase of [3H] spiroperidol binding was detected in the group of senescent animals. On the other hand, [3H] GABA binding is significantly decreased in substantia nigra and hypothalamus of aged rats, while it is unmodified in cerebral cortex, cerebellum, striatum and nucleus accumbens.

Aging↗
PubMed1980

Effect of chronic lead treatment on GABA-ergic receptor function in rat brain.

The effect of chronic lead treatment on brain gamma-amino-butyric acid (GABA)-ergic function has been studied in an attempt to correlate the clinical aspects of the chronic exposure to the metal with specific neurochemical alterations. [3H]GABA-specific binding and cyclic guanosine monophosphate (GMP) content have been measured in various rat brain areas and have been found to be increased in cerebellum and decreased in the striatum of rats after chronic lead treatment. The changes found in the GABA-ergic neurons were correlated with the different levels of lead exposure in rats. Our results indicated that lead selectively affects GABA-ergic function in various rat brain areas, inducing effects which are dose-dependent.

Animals↗