Effect of Δ9-tetrahydrocannabinol on monoamine oxidase activity of rat tissues in vivo

Inhibition of monoamine oxidase activity by cannabinoids

Abstract: Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and psychotropic drugs, including cannabinoids. This study investigated in vitro effects of cannabinoids on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters and affecting brain development and function. The effects of the phytocannabinoid Δ9-tetrahydrocannabinol (THC), the endocannabinoid anandamide (N-arachidonoylethanolamide [AEA]), and the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) on the activity of MAO were measured in a crude mitochondrial fraction isolated from pig brain cortex. Monoamine oxidase activity was inhibited by the cannabinoids; however, higher half maximal inhibitory concentrations (IC50) of cannabinoids were required compared to the known MAO inhibitor iproniazid. The IC50 was 24.7 μmol/l for THC, 751 μmol/l for AEA, and 17.9 μmol/l for WIN when serotonin was used as substrate (MAO-A), and 22.6 μmol/l for THC, 1,668 μmol/l for AEA, and 21.2 μmol/l for WIN when phenylethylamine was used as substrate (MAO-B). The inhibition of MAOs by THC was noncompetitive. N-Arachidonoylethanolamide was a competitive inhibitor of MAO-A and a noncompetitive inhibitor of MAO-B. WIN was a noncompetitive inhibitor of MAO-A and an uncompetitive inhibitor of MAO-B. Monoamine oxidase activity is affected by cannabinoids at relatively high drug concentrations, and this effect is inhibitory. Decrease of MAO activity may play a role in some effects of cannabinoids on serotonergic, noradrenergic, and dopaminergic neurotransmission.

Low platelet monoamine oxidase activity and chronic marijuana use

Abstract: Mean platelet monoamine oxidase (MAO) activity in 26 consecutively-studied male marijuana smokers was significantly lower than in a comparable group of non-marijuana smoking males. In addition, the level of current marijuana use reported by the subjects was significantly and inversely correlated with MAO activity. No acute reduction in MAO activity was found in response to smoking a marijuana cigarette containing 15 mg of delta-9-THC. Significant in vitro inhibition of MAO activity by THC was detected only at THC concentrations above 10−5M, approximately 100 times the peak plasma concentrations seen in vivo following smoking.

Effects of psychoactive drugs on cyclic nucleotides in the central nervous system.

Abstract: 1, Introduction 4 2. Notes on methodology 5 2,1, Whole cell preparat ions 5 2.2. Broken cellular preparations 5 2.3. lit vivo studies 6 2.3.1. Rapid fixation of tissues 6 2.3.2. hmtophores is 6 2.3.3. Direct electrical st imulation of adrenergic pathways 6 2.3.4. Intra-cerebro-ventricular drug administration 6 2.3.5. Body fluid measurements 7 2.3.6. Postmortem assays 7 2.3.7. His tochemical immunof luorescent techniques 7 3. Adenylate cyclase 7 3.1. Distribution and cellular localization 7 3.2. Development and aging of adenylate cyclase 8 3.2.1. Cyclic A M P levels 8 3.2.2. Adenylate cyclase 8 3.2.3. Catalytic and GTP sites 9 3.2.4. Adenosine and depolarizing agents 9 3.2.5. Adrenergic systems 10 3.2.6. Dopamine 11 3.2.7. Serotonin 12 3.2.8. Histamine 13 3.2.9. Metabolic role of cyclic AM P in development 13 3.2.10. Conclusions 14 3.3. Ionic requirements 14 3.4. Catalytic site 14 3.5. Transducer-GTP-sensi t ive site 15 3.6. Activation of adenylate cyclase 15 3.6.1. Adrenergic agents 15 3.6.2. Dopamine 17 3.6.3. Histamine 17 3.6.4. Serotonin (5-HT) 18 3.6.5. Prostaglandins 19 3.6.6. Adenosine 19 3.6.7. Amino acid transmitters 20 3.6.8. Depolarizing agents 21 3.6.9. Electrical st imulation 21 3.6.10. Steroids 21 3.6.11. Peptides 23 4. The phosphodiesterases and calmodulin 23 4.1. Distribution and localization 23 4.2. Development and aging 23 4.3. Properties and enzyme subtypes 25 4.4. Calmodulin 26 4.5. Regulation of phosphodiesterases 26 5. Guanylate cyclase-cyclic GMP 26 5.1. Distribution 26 5.2. Development and aging 27 5.3. Properties and enzyme subtypes 27 5.4. Activators and inhibitors of cyclic GMP 28 5.5. Regulation of cyclic GM P 28

Environmental stress as a factor in the response of rat brain catecholamine metabolism to Δ8-tetrahydrocannabinol

Abstract: In rats housed normally (aggregated, food and water ad lib) for fourteen days Δ8-tetrahydrocannabinol (THC) produced mild sedation and minimal hypothermia. An increase in noradrenaline synthesis was observed, but brain dopamine metabolism was unchanged. In rats removed from this ‘normal’ environment to conditions of isolation and food deprivation for 24 h THC produced immobility, marked hyper-reactivity, and hypothermia. Brain noradrenaline metabolism was unchanged by THC under these conditions, but significant changes in striatal dopamine metabolism were observed. These changes are consistent with increased dopamine reuptake in striatum produced by this combination of THC and novel environment. It is suggested that some of the behavioural effects of cannabis administered under stressful conditions may be related to alterations in striatal dopamine metabolism.

Determination of serum proteins by means of the biuret reaction.

Abstract: In the course of an investigation of the biochemical changes following experimental liver injury we felt the need of a simple, rapid, and accurate method for determining the protein fractions in small amounts of serum. Among the simpler procedures known, the biuret reaction seemed to offer the most encouraging possibilities. Variations and improvements in the application of the biuret reaction to clinical chemistry can be traced in the works of Autenrieth (l), Hiller (2), Fine (3), Kingsley (4), and Robinson and Hogden (5). Kingsley (6) simplified the technique by adding serum directly to a “one piece” reagent. Efforts have been made to increase the stability of such biuret reagents with ethylene glycol (7), tartrate (8), and citrate (9)) We began our investigation with Kingsley’s (6) method and report briefly on the two main difficulties encountered in its use. The first is that the total protein (TP) reagent and, to a lesser extent, the albumin (ALB) reagent are not sufficiently stable. The length of time they remain so depends upon the technique of their preparation. One consequence of this variable stability is a difficulty in duplicating calibration curves with different lots of reagent. Errors may arise when results with a new reagent are read from an old calibration curve. Serious errors occur if a reagent is used after the separation of any black deposit gives evidence of deterioration. A second difficulty has been that total protein estimations made with the TP reagent and read, as prescribed, from calibration curves prepared with the ALB reagent have tended to be too low. Recorded in Table I are the results of a number of analyses in which Kingsley’s biuret procedure has been compared with the Kjeldahl method2 on both normal and ab-

1-δ9-Tetrahydrocannabinol: Neurochemical and Behavioral Effects in the Mouse

Abstract: Administration of pure 1-delta(9)-tetrahydrocannabinol to mice had the following dose-dependent nzeurochemical and behavioral effects: a slight but significant increase in concentrations of 5-hydroxytryptamine in whole brain; a decrease in concentration of norepinephrine in brain after administration of low doses and an increase after high doses; diminished spontaneous activity, mloderate hypothermnia, hypersetisitivity to tactile and auditory stimiuli, and ataxia after low doses; and sedation, pronounced hypothermia, and markedly diminished spon taneous activity and reactivity after high doses. The duration of the effects on body temperature and spontaneous activity correlated generally with the changes in brain amines. The characteristic changes in brain amines do not correspond exactly to those observed with other psychotropic drugs.

A colorimetric method for the estimation of monoamine oxidase.

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Human blood platelet monoamine oxidase.

Abstract: Human blood platelet monoamine oxidase (MAO; EC 1.4.3.4) has been solubilized and purified about 12-fold. In contrast with MAO from other human tissues previously investigated, the enzyme is electrophoretically homogeneous and has a molecular weight of 235, 000. Its substrate specificities are similar to those of plasma benzylamine oxidase but its lack of sensitivity to isoniazid and semicarbazide distinguishes it from the plasma enzyme. The differences between the physicochemical properties of platelet MAO and isoenzymes from other anatomical sites suggests that the platelet enzyme is unlikely to provide a satisfactory index of in vivo activity in the whole organism.