Download Cyclic Nucleotides in the Nervous System by John Daly PDF

By John Daly

The elucidation of the mobile and molecular bases underlying the inte­ grated functionality of the imperative worried procedure, either in illness and in healthiness, needs to finally come from the mixed efforts of scientists from many disciplines, together with biology, chemistry, histology, pathology, body structure, pharmacology, and psychology. conversation among scientists from those a variety of disciplines-vital to the development of our realizing of the functionality of the apprehensive system-has turn into a growing number of tough lately. either expanding specialization and the terrific raises in guides pertinent to mind study in a large spectrum of journals, in symposium volumes, in monographs, in abstracts, and in experiences contrib­ ute to the issues of cross-communication or even of conversation inside a systematic self-discipline. learn at the value of cyclic nucleo­ tides to the functionality of apprehensive structures is especially illustrative of the conversation challenge. because the preliminary guides by way of Sutherland, Rall, and Butcher within the past due fifties and early sixties on excessive degrees of adenylate cyclase, phosphodiesterases, and cyclic AMP in mind, the consequent litera­ ture of this box has increased exponentially. today, from 5 to 10 guides suitable to cyclic nucleotides and the frightened procedure look each one week. certainly, those are minimum numbers established quite often on exam of literature titles and key index phrases. Many articles all in favour of a few point of crucial functionality comprise, buried inside their textual content, experiments with or relating to cyclic nucleotides.

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Theophylline (K i , 35 ILM) competitively inhibited the response to 2-chloroadenosine, while having no effect on prostaglandin-sensitive cyclase activity. 2' - and 5' -deoxyadenosine inhibited basal, 2-chloroadenosine, and prostaglandinsensitive cyclases. Prostaglandins El and E2 caused a very large activation of cyclases from neuroblastoma cells, while prostaglandin F2

Both adenosine and exogenous cyclic AMP elicited a 2-fold increase in radioactive cyclic AMP in hippocampal preparations. In one experiment, epinephrine elevated endogenous levels of cyclic AMP in cerebellar preparations by 32-fold while elevating radioactive cyclic AMP by 17-fold. The effects of epinephrine in cerebellar preparations were antagonized by a ~-antagonist, propranolol, while in cortical preparations an a-antagonist, dibenamine, was most effective. The stimulatory effects of adenosine (EC so, 10 JLM) and cyclic AMP were antagonized by theophylline.

Levels of high Km cyclic AMP-phosphodiesterase were stated to be similar in brain homogenates from mouse, rat, rabbit, steer, sheep, and chicken (Breckenridge and Johnston, 1969). Levels of phosphodiesterase were in most species high in gray matter of cortex and in hypothalamus, lower in cerebellum, medulla, and pons, and very low in spinal cord. In rat brain a sixfold range of low Km cyclic AMPphosphodiesterase was observed with levels decreasing in the following order: neocortex, hippocampus> caudate nucleus, septum-fornix> olfactory tubercle, thalamus, hypothalamus> olfactory bulb> medulla-pons, cerebellum, spinal cord (Weiss and Costa, 1968).

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