Effects of psychoactive drugs on cyclic nucleotides in the central nervous system.
TL;DR: The aim of these studies was to establish a baseline level of understanding of the role of adrenergic pathways in the development and aging of cyclic GMP, as well as to provide a baseline for the regulation of phosphodiesterases and inhibitors.
About: This article is published in Progress in Neurobiology.The article was published on 1983-01-01. It has received 34 citations till now.
Citations
More filters
TL;DR: In this article, the authors propose a method to identify the root cause of a problem.Abbreviations: [2]... ].., [3]
463 citations
TL;DR: The results point to an important role for cGMP in the functioning of glial tissue in the cerebellum and also suggest a role for nitric oxide as an intercellular mediator in the functions of glutamate and ANF in the Cerebellum.
Abstract: In this study we describe the localization of formaldehyde-fixed cGMP-immunoreactivity (cGMP-IR) in rat cerebellar tissue slices incubated in vitro. In the absence of phosphodiesterase inhibition, cGMP-immunofluorescence was of low intensity in tissue slices prepared from immature cerebella. Addition of isobutylmethylxanthine (IBMX) to the incubation medium resulted in the appearance of cGMP-IR in clusters of astrocytes in the internal granular layer. Addition of N-methyl-d-aspartate (NMDA), kainic acid, atrial natriuretic factor (ANF), or sodium nitroprusside (SNP) gave an intense cGMP-IR in Bergmann fibres, Bergmann cell bodies, and astrocytes in the internal granular layer. Astrocytes in the white matter showed cGMP-IR after incubation of the slice in the presence of ANF or nitroprusside, but not after NMDA or kainic acid. In addition, after SNP stimulation of cGMP production, cGMP-IR was found in fibres which were not positive for glial fibrillary acidic protein (GFAP). In the adult cerebellar slice, intense basal cGMP-immunostaining was observed in Bergmann fibres, Bergmann cell bodies, and astrocytes in the granular layer. No cGMP-IR was observed in Purkinje cells. Stimulation of the cGMP-content in the glial structures by NMDA, ANF, or SNP, was suggested by the immunocytochemical results. However, when measured biochemically, only the effect of SNP was statistically significant, and immunocytochemistry showed that SNP clearly stimulated cGMP synthesis in neuronal cell structures. In the cerebellum of the aged rat a reduced cGMP-IR was found compared to the adult, in the same structures which showed cGMP-IR in the adult. Basal cGMP-immunostaining was reduced in the presence of haemoglobin, methylene blue, by inhibiting nitric oxide synthesis with NG-monomethyl-l-arginine (NGMAr), or by depletion of external Ca2+. Also the stimulatory effect of NMDA and of ANF (partly) on the cGMP-IR was inhibited by these compounds. cGMP-IR after stimulation of guanylate cyclase by SNP was reduced by the concomitant presence of haemoglobin or methylene blue, but not by NGMAr, or by omission of Ca2+. Our results point to an important role for cGMP in the functioning of glial tissue in the cerebellum and also suggest a role for nitric oxide as an intercellular mediator in the functioning of glutamate and ANF in the cerebellum.
170 citations
TL;DR: A new-type highly specific antiserum is prepared, suitable to demonstrate cGMP-immunoreactivity in tissue material, and was prepared in a way which equals tissue fixation.
164 citations
TL;DR: It was found that spike-like transients were often present in the pyriform cortex EEG before kindling had begun, and these transients developed progressively into large amplitude and complex IIS as kindling proceeded.
105 citations
TL;DR: A comparison of the distribution of [3H] forskolin binding sites with those reported for several neurotransmitter receptor types indicated that forSkolin identified adenylate cyclase was probably not linked to any single type of neurotransmitter receptors.
77 citations
References
More filters
TL;DR: Pharmacological and biochemical criteria can be used to separate those dopamine receptors which are linked to the enzyme adenylyl cyclase and those which are not.
Abstract: Pharmacological and biochemical criteria can be used to separate those dopamine receptors which are linked to the enzyme adenylyl cyclase and those which are not.
3,746 citations
TL;DR: Cell membrane receptors for hormones and neurotransmitters form oligomeric complexes with GTP-regulatory proteins and inhibit the latter from reacting with G TP, and this theory may apply generally to membrane signal transduction involving surface receptors.
Abstract: Cell membrane receptors for hormones and neurotransmitters form oligomeric complexes with GTP-regulatory proteins and inhibit the latter from reacting with GTP. Hormones and neurotransmitters act by releasing the inhibitory constraints imposed by the receptors, thus allowing the GTP-regulatory proteins to interact with and control the activity of enzymes such as adenylate cyclase. This theory may apply generally to membrane signal transduction involving surface receptors.
1,686 citations
TL;DR: The Medical Journal of Australia as discussed by the authors republish Cade's seminal paper and acknowledge their debt to The Medical Journal for allowing us to reprint the article from their September 1949 issue.
Abstract: Dr John Cade, one of the most distinguished Australian psychiatrists, died in November, 1980. We republish his seminal paper and acknowledge our debt to The Medical Journal of Australia for allowing us to reprint the article from their September 1949 issue.
1,123 citations
TL;DR: Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidols, which may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.
Abstract: Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidol. This increase in receptor sites may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.
993 citations