Julius Axelrod

A simple and rapid method for injecting H3-norepinephrine into the lateral ventricle of the rat brain

Abstract A simple and direct method of labelling brain norepinephrine stores, via injection into the lateral ventricle is described. H 3 -norepinephrine introduced by this procedure was found to be distributed evenly in both sides of the brain. The accumulation of H 3 -norepinephrine in various brain regions parallels that of endogenous levels of norepinephrine and the amine is selectively localized in the “nerve endings”. The disappearance of H 3 -norepinephrine administered by the direct injection technique and its modification by drugs are similar to that of material introduced by stereotaxic procedures.

A sensitive and specific fluorescence assay for tissue serotonin

Abstract A sensitive and specific method for the estimation of serotonin in biological materials is described. In this method, serotonin is reacted with ninhydrin to form a product whose fluorescence is eight times more intense than the native fluorescence of serotonin in strong acid solution. With this method it is possible to measure serotonin in organs in which endogenous serotonin had not been previously detected and to study the subcellular distribution of this amine in the rat pineal and adrenal glands.

Norepinephrine and dopamine content of hypothalamic nuclei of the rat

Abstract The concentrations of norepinephrine and dopamine of 27 isolated rat hypothalamic nuclei or nuclear subdivisions have been determined using an enzymatic-isotopic assay. The hypothalamic nuclei contain 3–20 times more NE and DA than is measured in the cortex. They are distributed unevenly throughout the hypothalamus and individual hypothalamic nuclei are heterogenous as regards their content of the amines. The dopamine content of the median eminence is among the highest measured in the brain (65 ng/mg protein). The norepinephrine content is about half that of dopamine. All of the hypothalamic nuclei contain dopamine. It is highly concentrated in the rostral subdivisions of the arcuate nucleus, the paraventricular and dorsomedial nuclei, the retrochiasmatic area, the medial posterior subdivision of the ventromedial nucleus and in the medial forebrain bundle at the posterior hypothalamic level. The highest concentrations of norepinephrine were found in the paraventricular and dorsomedial nuclei and in the retrochiasmatic area. The rostal subdivision of the arcuate nucleus and the periventricular and preoptic suprachiasmatic nuclei are also rich in norepinephrine. The posterior hypothalamus (premammillary nuclei, caudal subdivision of the arcurate nucleus, posterior hypothalamic nucleus) contains norepinephrine and dopamine in relatively low concentrations.

Receptor-mediated activation of phospholipase A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers

Abstract GTP-binding (G) proteins transduce receptor-mediated signals for a variety of effector systems (adenylate cyclase, cyclic nucleotide phosphodiesterases, ion channels and phospholipase C). This review describes another effector system that is linked to a G protein — phospholipase A 2 . Upon activation of phospholipase A 2 by a receptor-coupled G protein, arachidonic acid and its numerous biologically active metabolites are generated. Arachidonic acid as well as some of the arachidonate metabolites can act as first and second messengers. In some cases, arachidonate and its metabolites interact with other transducing systems to modulate or amplify their signals.

Localizing tritiated norepinephrine in sympathetic axons by electron microscopic autoradiography.

Following intravenous infusion of tritiated norepinephrine, rat pineals were prepared for combined autoradiography and electron microscopy. Concentrations of photographic grains were observed only over regions of preterminal autonomic axons containing granulated vesicles, thereby directly demonstrating uptake of norepinephrine into these axons and strongly suggesting that their granulated vesicles contain norepinephrine.

Melatonin Synthesis in thePineal Gland: Control by Light

In rats placed in continuous darkness for 6 days, there is a striking increase in the activity of melatonin-synthesizing-enzyme (hydroxyindole-0-methyl transferase) in the pineal gland, but no change in the activity of monoamine oxidase. Since melatonin appears to have a hormonal role in mammals, and its synthesis is confined to the pineal gland, the inhibition of hydroxyindole-O-methyl transferase by light may constitute a mechanism of neuroendocrine regulation.

Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline☆

Abstract Species and strain differences in response to hexobarbitone and presumably to antipyrine, amidopyrine and other drugs can be expressed largely in terms of the activities of the drug-transforming enzymes in microsomes. However, variation in the inherent sensitivity of the central nervous system may also be a factor. The sex difference in the rat in response to hexobarbitone and presumably to other drugs is also a reflection of the activity of the enzyme system in liver microsomes. Sex hormones have a role in regulating sex difference in drug metabolism. The guinea pig and mouse show no sex difference in the metabolism of hexobarbitone. Implications of these findings to drug action and to the development of new drugs are discussed.

Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat

Anandamide (arachidonylethanolamide) is a novel lipid neurotransmitter first isolated from porcine brain which has been shown to be a functional agonist for the cannabinoid CB1 and CB2 receptors. Anandamide has never been isolated from human brain or peripheral tissues and its role in human physiology has not been examined. Anandamide was measured by LC/MS/MS and was found in human and rat hippocampus (and human parahippocampal cortex), striatum, and cerebellum, brain areas known to express high levels of CB1 cannabinoid receptors. Significant levels of anandamide were also found in the thalamus which expresses low levels of CB1 receptors. Anandamide was also found in human and rat spleen which expresses high levels of the CB2 cannabinoid receptor. Small amounts of anandamide were also detected in human heart and rat skin. Only trace quantities were detected in pooled human serum, plasma, and CSF. The distribution of anandamide in human brain and spleen supports its potential role as an endogenous agonist in central and peripheral tissues. The low levels found in serum, plasma, and CSF suggest that it is metabolized in tissues where it is synthesized, and that its action is probably not hormonal in nature.

Proportional Release of Norepinephrine and Dopamine-β-Hydroxylase from Sympathetic Nerves

Dopamine-β-hydroxylase(DBH), the enzyme that catalyzes the conversion of dopamine to norepinephrine, is localized in the vesicles containing catecholamine in sympathetic nerves. This enzyme is released with norepinephrine when the nerves to the guinea pig vas deferens are stimulated in vitro, and the amount of enzyme discharged increases as the length of stimulation periods increases. The amount of DBH released is proportional to the amount of norepinephrine released, and the ratio of norepinephrine to DBH discharged into the incubation medium is similar to that in the soluble portion of the contents of the synaptic vesicles from the vas deferens. These data are compatible with the release of the neurotransmitter norepinephrine and DBH from symnpathetic nerves by a process of exocytosis.

Enzymatic O-Methylation of N-Acetylserotonin to Melatonin

An enzyme, hydroxyindole-O-methyl transferase, that can transfer the methyl group of S-adenosylmethionine to the hydroxy group of N-acetylserotonin to form the hormone melatonin is described. This enzyme, which is highly localized in the pineal gland, also O-methylates serotonin.