Introduction to synaptic circuits, Gordon M.Shepherd and Christof Koch membrane properties and neurotransmitter actions, David A.McCormick peripheral ganglia, Paul R.Adams and Christof Koch spinal cord - ventral horn, Robert E.Burke olfactory bulb, Gordon M.Shepherd, and Charles A.Greer retina, Peter Sterling cerebellum, Rodolfo R.Llinas and Kerry D.Walton thalamus, S.Murray Sherman and Christof Koch basal ganglia, Charles J.Wilson olfactory cortex, Lewis B.Haberly hippocampus, Thomas H.Brown and Anthony M.Zador neocortex, Rodney J.Douglas and Kevan A.C.Martin Gordon M.Shepherd. Appendix: Dendretic electrotonus and synaptic integration.

The synaptic organization of the brain

A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological concentrations of free Ca2+ and is inhibited by NG-monomethyl-L-arginine, but not by its enantiomer NG-monomethyl-D-arginine or by L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, or L-arginine methyl ester can replace L-arginine as substrates for the enzyme. These results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to our hypothesis that the formation of NO from L-arginine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase.

https://www.pnas.org/content/pnas/86/13/5159.full.pdf

Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.

When horseradish peroxidase is injected into the optic tectum of a chick, axons of ganglion cells transport it centripetally to their cell bodies in the retina at a rate of about 72 millimeters per day. After intraocular injections in the young chick, the peroxidase is transported centripetally along efferent axons, and is concentrated in cell bodies within the isthmo-optic nucleus. This retrograde movement of protein from axon terminal to cell body suggests a possible mechanism by which neurons respond to their target areas.

http://science.sciencemag.org/content/sci/176/4042/1416.full.pdf

Retrograde Axonal Transport in the Central Nervous System

The role of adenosine and its nucleotides in central synaptic transmission.

The formation of nitric oxide (NO) from the amino acid L-arginine not only explains the biological properties of the so-called endothelium-derived relaxing factor (EDRF) but also accounts for the stimulation of the soluble guanylate cyclase in a number of tissues such as the platelet and the brain. Furthermore, NO is a cytotoxic factor released by murine macrophages and other cells following immunological activation. Nitric oxide is synthesized by an enzyme, the NO synthase, of which two types have been identified. One type is constitutive and is responsible for the release of NO for physiological transduction purposes, while the other is induced by cytokines and releases NO as part of the immunological response.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2362.1991.tb01383.x

Endogenous nitric oxide: physiology, pathology and clinical relevance.

Growth stimulated by protease treatment of untransformed cells is correlated with a decrease in cell cAMP levels and can be prevented by dibutyryl cAMP. The changed growth characteristics of transformed cells are discussed with regard to cAMP levels.

Growth Control and Cyclic Alterations of Cyclic AMP in the Cell Cycle

The frequency of miniature endplate potentials (mepps) in rat diaphragms was markedly increased by epinephrine and norepinephrine in preparations exposed to 15 mM K+. The effect was rapid in onset but gradually declined during continued exposure to the catecholamines. N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl-cAMP) also caused transient frequency increases resembling in time-course those observed with catecholamines. Contrary to previous reports, catecholamines and dibutyryl-cAMP had little effect on mepp frequency in preparations not treated with K+. Sustained increases with theophylline and decreases with adenosine were found in both K+-treated and untreated preparations. Analysis of the data obtained with catecholamines showed the intensity of the response to be a function of nerve terminal polarization. The inability of catecholamines and dibutyryl-cAMP to affect mepp frequency of untreated preparations argues against an obligatory role for cAMP in the neurosecretory mechanism. The findings are consistent with an action of catecholamines and cAMP in the regulation of transmitter release at fatigued preparations.

/pdf/a-cyclic-adenosine-monophosphate-link-in-the-catecholamine-2cl3qwwl32.pdf

A cyclic adenosine monophosphate link in the catecholamine enhancement of transmitter release at the neuromuscular junction.

Reversed polarity of rapid axonal transport in chicken motoneurons.

Adenosine 3',5'-Monophosphate in Glial Tumor Cells ALTERATIONS BY 5-BROMODEOXYURIDINE

C-6 astrocytoma cells respond to 0.1 mM norepinephrine by a greater than 200-fold elevation of adenosine cyclic 39, 59-monophosphate (cAMP) and an 80% degradation of glycogen during 20 min of incubation in Ham’s F-10 medium. Evaluation of the time course of these effects indicated that glycogenolysis occurred nonlinearly at a rate of 1-2 nmoles/min/mg of protein; cAMP was maximally elevated after 5 min of incubation and remained so for the 30-min experiment. Norepinephrine induced transformation of glycogen phosphorylase to the 39-AMP-independent or a form during the first 30 sec of incubation. At the time when phosphorylase a formation had begun, 5 sec after norepinephrine addition, cAMP was elevated only 10-fold. During a 3-hr treatment of cells with norepinephrine, cAMP and glycogen concentrations returned to nearly control concentrations; yet incubation fluid retained sufficient norepinephrine to elevate cAMP as before in fresh samples of cells. Treatment of C-6 cells with norepinephrine for 3 hr followed by 1 hr of incubation without hormone largely suppressed the effect of a second norepinephrine treatment on cAMP concentration, but glycogenolysis occurred as before. 1-Methyl-3-isobutylxanthine, an inhibitor of cAMP phosphodiesterase, partially overcame the suppression of the norepinephrine effects when added with norepinephrine. It is concluded that C-6 astrocytoma cells contain a norepinephrine-activated system of enzymes for degrading glycogen and that norepinephrine treatment modifies the response of the cells to subsequent exposure to this neurohormone.

Bruce McL. Breckenridge

Papers

Growth Control and Cyclic Alterations of Cyclic AMP in the Cell Cycle

A cyclic adenosine monophosphate link in the catecholamine enhancement of transmitter release at the neuromuscular junction.

Reversed polarity of rapid axonal transport in chicken motoneurons.

Adenosine 3',5'-Monophosphate in Glial Tumor Cells ALTERATIONS BY 5-BROMODEOXYURIDINE

Norepinephrine-sensitive properties of C-6 astrocytoma cells.