Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYRAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources
PubMed2004

[Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma].

OBJECTIVE: To investigate the possibility of using radioiodine labeled framework region (FR) antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. METHODS: A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5' with a tyramine group which was further radioiodinated. Radioiodination of the tyramine derivatized oligonucleotides was performed using the chloramine T method. (1) Normal CD-1 mice were injected via a tail vein with 148 kBq (125)I-FR-ASON (2-3 microg). Animals were sacrificed at the end of 1, 2, 4 and 24 h, and tissue samples were studied.(2) Liposome-mediated 3.33 MBq (131)I-FR-ASON (7-9 microg) were injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 107 Namalwa cells) meanwhile liposome-mediated (131)I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. RESULTS: The 5' tyramine group allowed specific and stable radiolabeling of the ASON with radioiodine. The radioactivity reached its peak 1 h after injection, and then decreased rapidly in normal mice after intravenous administration of (125)I-FR-ASON. The liver, stomach and intestine played an important role in biodistribution and radioactivity counts were low in bone, brain and blood. When (131)I-FR-ASON was injected intratumorally into mice grafted with Namalwa cell line, images showed the tracer accumulated in the tumor. Immediately after intratumoral administration, only the tumor was visible. Scintiscans performed at the end of 1 and 2 h showed elimination of the tracer from the tumor to the abdomen and at the end of 24 h the tumor was clearly seen. Percentage of the injected dose per gram of tumor and T/NT ratios for the sense group (control) were significantly lower than those of the antisense group. CONCLUSION: Radiolabeled Ig FR ASON showed high specificity in V1 family B-cell lymphoma, which should be further investigated for nuclear medicine imaging application and radionuclide antisense therapy.

Animals↗
PubMedDate not supplied

[The role of monoamine oxidase in the regulation of mitochondrial energy functions].

Incubation of aldehyde dehydrogenase-free mitochondrial preparations with biogenic amines serotonin, tyramine, 2-phenylethylamine and 5-methoxytryptamine resulted in inhibition of enzymes activity of both outer (rotenone-insensitive NADH-cytochrome c reductase) and inner (succinate dehydrogenase, succinate cytochrome c reductase) mitochondrial membranes. Solubilization of mitochondria after the incubation did not influence the amine-induced alteration of succinate dehydrogenase activity. Pretreatment of the organelles with a mixture containing chlorgyline and deprenyl completely inhibited monoamine oxidase (MAO) activity and prevented the effects of all the amines studied on mitochondrial enzymes. MAO-dependent effects of 5-methoxytryptamine were fully reproduced by 5-methoxyindolyl-3-acetaldehyde (one of probable products of 5-methoxytryptamine deamination). The effect of the aldehyde was not prevented by chlorgyline and deprenyl. After selective inhibition of MAO-A by chlorgyline the order of MAO-B-dependent effects of biogenic amines on mitochondrial enzymes studied was as follows: tyramine greater than or equal to 2-phenylethylamine much greater than serotonin. In deprenyl pretreated mitochondria the potency of MAO-A-dependent effects of these amines was: serotonin greater than tyramine much greater than much greater than 2-phenylethylamine. The data obtained suggest that the product(s) of oxidative deamination of biogenic amines (probably the aldehydes) catalyzed by both types of MAO (MAO-A and MAO-B) are able to regulate the energy functions of mitochondria.

Animals↗
PubMed1990

Rapid enzymatic analysis of plasma for tyrosine.

In this rapid, simple, and convenient enzymatic method for measurement of tyrosine in plasma, tyrosine is converted to tyramine by action of tyrosine decarboxylase (EC 4.1.1.25) and the tyramine produced is oxidized to p-hydroxybenzyl aldehyde and hydrogen peroxide by action of tyramine oxidase (EC 1.4.3.9). The hydrogen peroxide is reacted with 4-aminoantipyrine and N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine in the presence of peroxidase (EC 1.11.1.7) to obtain quinoneimine dye, the absorbance of which is measured at 570 nm. Thus tyrosine is measured in the visible range. The CV was 4.6% or less, and the measurement was unaffected by other amino acids, except for phenylalanine. The values obtained (y) correlated well with those obtained with an amino acid analyzer (x): y = 0.902x + 3.92 mumol/L (Syx = 12.3; r = 0.985; n = 54).

Autoanalysis↗
PubMed1990

Improving the tumor retention of radioiodinated antibody: aryl carbohydrate adducts.

Improved methods for attaching radioiodine to monoclonal antibodies have been developed. Ten aryl carbohydrate adducts were synthesized by the reductive amination of a carbohydrate with an aryl amine, using sodium cyanoborohydride as a reducing agent. After purification by chromatography and characterization by nuclear magnetic resonance they were iodinated using the chloramine-T method. Iodinated adducts were activated with cyanuric chloride and incubated with protein at room temperature. The immunoreactivity and avidity of radioiodinated tyramine cellobiose (TCB) labeled antibody were fully preserved when compared to electrophilically radioiodinated antibody. Radioiodinated TCB-and tyramine glucose-labeled monoclonal antibodies showed much greater intracellular retention of radioiodine when compared to electrophilically radioiodinated monoclonal antibodies. Neither radioiodinated tyramine nor radioiodinated TCB had any specific tissue uptake or retention. In mice the retention of radioiodinated TCB labeled anti-Thy-1.1 antibody (1A14) by Thy-1.1-bearing lymphoma cells was 2 times greater than that of chloramine-T labeled 1A14 antibody, whereas the plasma clearance curve and uptake in normal tissues was not changed. This method of radioiodinating monoclonal antibodies increases the retention time of radioiodine in tumor and thus may obviate the problem of intracellular deiodination, a perceived disadvantage of electrophilically iodinated antibodies, with respect to tumor retention of radioactivity.

Animals↗
PubMed1989

[Comparison of the new MAO-A inhibitors moclobemide, brofaromine and toloxatone with tranylcypromine in an animal experiment: significance for clinical practice].

The rat studies presented in this manuscript show that the new non-hydrazine compounds moclobemide, brofaromine and toloxatone have a profile typical of monoamine oxidase-A (MAO-A) inhibitors. These inhibitors are short-acting (16-24 h), reversible, non-hepatotoxic and have only low liability to potentiate tyramine pressor effects (cheese-effect). The present results in rats and the clinical trials provide evidence that moclobemide is an orally active MAO-A inhibitor which, due to its remarkably low tyramine potentiating pressor effects and to its lack of anticholinergic activity, has a very attractive pharmacological profile. In contrast to moclobemide, tranylcypromine is an irreversible and mixed MAO-A and MAO-B inhibitor with long-lasting effects. This hydrazine derivative is not devoid of hepatotoxic effects and markedly potentiates tyramine pressor effects. Moclobemide, being a particularly safe MAO-A inhibitor, seems to be an effective new compound for the therapy of exogenous and endogenous depressive states.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Effect of heavy metal salts on rat brain and liver monoamine oxidase activity.

In experiments on male Wistar albino rats was studied the effect of Co, Cd, Ni, Zn, Hg and Pb on the activity of rat liver and brain monoamine oxidase (MAO) using tyramine, serotonin and beta-phenylethylamine as substrates. It was established that ZnSO4 significantly increased the activity of liver MAO with all substrates studied, Co(NO3)2 increased it when tyramine and serotonin were used while NiSO4 increased MAO activity when serotonin was used as a substrate. All metals studied did not change MAO activity in the brain except for Co(NO3)2 which significantly increased the enzyme activity with tyramine as a substrate. The activity of liver MAO proved to be more susceptible to heavy metals after subchronic exposure than that in the whole brain.

Animals↗
PubMedDate not supplied

[Defect in deamination of biogenic amines in spontaneous hypertension].

Activity of monoamine oxidases (MAO) of the types A and B (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) has been studied in mitochondrial fractions from brain, heart, liver and kidney of 24-week-old rats of the normotonic strain Wistar Kyoto (WKY) and spontaneously hypertonic rats (SHR). As compared with the WKY rats, in the SHR strain the activity of MAO-A in heart mitochondria was increased 1.5-1.7-fold; in liver mitochondria the activities of both MAO-A and -B were increased 2.6-2.7-fold. In brain mitochondria there was noted only slight tendency towards an increase in MAO-A (substrate: 5-hydroxytryptamine) and MAO-B (substrate: 2-phenylethylamine) activities in the SHR strain as compared with the normotonic animals of the same age. However, in experiments with tyramine as a substrate of MAO the enzymatic activity in SHR brain mitochondria was increased 1.5-fold (P less than 0.05) as compared with the WKY rats. In kidney mitochondria of SHR the activity of MAO (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) did not exhibit any alterations as compared with the control WKY rats.

Animals↗
PubMed1965

Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances.

Monoamine oxidase inhibitors (MAOI) in clinical use have an irreversible action on MAO, and this persists until the enzyme has been resynthesized. The effects of small daily doses of MAOI are therefore cumulative. The biochemical effects of these drugs will involve several substrates of MAO, e.g. dopamine, tyramine, serotonin and, to a lesser extent, noradrenaline and adrenaline.MAO probably regulates the metabolism of catecholamines and serotonin in tissues, while catechol-O-methyltransferase is responsible for the metabolism of circulating noradrenaline and adrenaline.Certain pharmacological effects of MAOI are related to the accumulation of monoamines in various tissues that follows the decrease of intraneuronal deamination. Among these effects are reversal of the reserpine syndrome in animals and augmentation of the pharmacological action of monoamines. Other effects are unrelated to the inhibition of MAO, e.g. immediate desynchronization of EEG and initial pressor effects.MAOI may potentiate or change the action of several other drugs and even certain foods. The mechanisms involved are usually reasonably predictable from animal experiments. Substrates of MAO, e.g. dopamine and tyramine, evoke augmented and prolonged effects in patients treated with MAOI. This is partly due to an impaired metabolism of the circulating amines. In addition, inhibition of intestinal and hepatic MAO largely increases the absorption of tryamine from cheeses and other foods. Usually innocuous amounts of tyramine may therefore cause hypertensive reactions in patients treated with MAOI. Indirectly acting sympathomimetic amines, such as amphetamines, ephedrine and MAOI with amphetamine-like properties, can be potentiated, because they may release increased amounts of nor-adrenaline from sympathetic nerve endings after MAO inhibition. The effects of any amine, whether a substrate of MAO or not, may be enhanced by MAO inhibitors producing postganglionic block. This is due to ;denervation' supersensitivity of adrenergic receptors.Harmful pharmacological interaction is also possible between MAO inhibitors and agents which release (reserpine) or replete (amine precursors, e.g. L-DOPA in broad beans) monoamines centrally and peripherally. Drugs that sensitize adrenergic and tryptaminergic receptors to the action of monoamines, e.g. imipramine-like compounds, may be greatly potentiated by MAO inhibitors. The anti-hypertensive effects of thiazides and ganglion-blocking agents may be enhanced by MAOI. A few drugs are known to exert prolonged effects in occasional patients treated with MAOI, e.g. pethidine, phenothiazines and pentobarbital. MAOI may possibly decelerate the metabolism of these compounds by a nonspecific inhibition of liver microsomal enzymes. Finally, a great number of agents have been found empirically to evoke augmented effects after inhibition of MAO, e.g. insulin and anti-Parkinson drugs.

Drug Synergism↗
PubMed1983

Tissue sites of degradation of apoprotein A-I in the rat.

The tissue sites of degradation of apoprotein A-I were determined in the rat in vivo using a newly developed tracer of protein catabolism, an adduct of 125I-tyramine and cellobiose. This methodology takes advantage of the fact that when a protein labeled with 125I-tyramine-cellobiose is taken up and degraded, the radiolabeled ligand remains trapped intracellularly. Thus, radio-iodine accumulation in a tissue acts as a cumulative measure of protein degradation in that tissue. In the present studies, apoprotein AI (apo-A-I) was labeled with tyramine-cellobiose (TC). The TC-labeled apo-A-I was then reassociated with high density lipoprotein (HDL) in vivo by injection into donor animals. After 30 min, serum from donor animals was recovered and then injected into recipient rats. TC-labeled apo-A-I in the donor serum was shown to be exclusively associated with HDL. The fractional catabolic rate of 125I-TC-apo-A-I was not significantly different from that of conventionally labeled apo-A-I. The kidney was the major site of degradation, accounting for 39% of the total. The liver was responsible for 26% of apo-A-I catabolism, 96% of which occurred in hepatocytes. The kidney was also the most active organ of catabolism/g of wet weight. The tissues next most active/g of wet weight were ovary and adrenal, a finding that is compatible with a special role of HDL in the rat for delivery of cholesterol for steroidogenesis. Immunofluorescence studies of frozen sections of rat kidney demonstrated the presence of apo-A-I on the brush-border and in apical granules of proximal tubule epithelial cells. Preliminary studies using HDL labeled both with 125I-TC-apo-A-I and [3H]cholesteryl ethers again demonstrated high rates of renal uptake of apo-A-I but less than 1% of total ether uptake. It is postulated that the high activity of kidney was not due to uptake of intact HDL particles, but rather, due to glomerular filtration and tubular reabsorption of free apo-A-I.

Animals↗
PubMedDate not supplied

[Decrease of placental amine oxidase activities in premature birth].

48 women with normal (38-40 weeks) and premature (38-37 weeks) labor were examined. The rate of deamination of serotonin, tyramine, beta-phenylethylamine, putrescine, cadaverine and histamine in samples containing extracts of the control group placenta averaged 0.86; 0.62; 0.18; 0.145; 0.63; 0.12 (nmoles NH3 per I mg of protein within I min), respectively. In the placental extracts obtained after the premature labor the rate of deamination of the substrates studied was decreased and constituted 0.4; 0.23; 0.108; 0.105; 0.29 and 0.084 nmoles NH3, respectively. The decrease in the rate of deamination of the amines studied, exhibiting high biological activity, appears to be responsible for premature labor. In the control group a correlation was found between the rates of serotonin and tyramine deamination as well as of putrescine and cadaverine deamination. The rates of deamination of mono- and diamines did not correlate. Deamination of beta-phenylethylamine and histamine did not depend also on deamination of other substrates studied. The data obtained demonstrate the presence in placenta of at least two forms of the enzymes, deaminating monoamines (one form for serotonin and tyramine and the other form for beta-phenylethylamine) as well as two forms of diamine oxidase - one form deaminating cadaverine and putrescine and the second form - histamine.

Amine Oxidase (Copper-Containing)↗
PubMed1983

[Effects of oxygen and drugs on monoamine oxidase in the dog liver].

The substrate specificity and effects of oxygen concentration and inhibitors on dog liver mitochondrial monoamine oxidase were investigated. MAO activity was determined by measuring oxygen uptake by Warburg's manometer. Dog liver mitochondrial MAO oxidized tyramine most strongly, but oxidation of serotonin, benzylamine and beta-phenylethylamine by this enzyme was found to be very weak, showing less than 30% that of tyramine oxidation. Clorgyline and harmine showed slight inhibition of oxidation of all substrates used in this experiment; however, deprenyl and pargyline strongly inhibited the oxidation of tyramine. The affinity of MAO towards oxygen was found to be strongest with benzylamine as substrate and weakest with hexylamine, and it was intermediate with serotonin. The differences in affinities towards oxygen of this enzyme with various substrates were not changed with any MAO inhibitors added to the reaction mixture. These results suggest that MAO in dog liver mitochondria belongs to type B MAO because of the characteristic behavior of this enzyme to inhibitors. It is suggested that the multiplicity of MAO, which is characterized by substrate and inhibitor specificities, is different from the multiplicity, which is characterized by the affinities towards oxygen.

Animals↗
PubMed1983

High pressure liquid chromatographic determination of putrefactive amines in foods.

A high pressure liquid chromatographic (HPLC) procedure is described for determining the following putrefactive amines: histamine, tyramine, putrescine, cadaverine, tryptamine, and beta-phenylethylamine. The amines were extracted from tuna or cheese with methanol. Further cleanup was performed by sequential extractions with butanol and HCl. The acid extract was dried, and residues were derivatized with dansyl chloride. HPLC separations were performed on an Ultrasphere-ODS column at 33 degrees C. A gradient elution program was used; the total elution time was less than 17 min. Linear standard curves with high correlation coefficients were obtained. The procedure allowed good recoveries of histamine, tyramine, putrescine, and cadaverine; recoveries of tryptamine and beta-phenylethylamine were lower but constant. With this method, some swiss cheese samples were found to contain considerable amounts of histamine, tyramine, putrescine, cadaverine, and beta-phenylethylamine. Canned tuna samples had very low levels of these amines. Since the presence of amines at high levels has been associated with tuna decomposition, this method may be useful in identifying decomposed fish.

Amines↗
PubMed1980

Dopamine beta-hydroxylase. Inactivation by a suicide substrate.

Dopamine beta-hydroxylase (EC 1.14.17.1) is inactivated by p-hydroxybenzylcyanide (PHBC) in a manner characteristic of a suicide substrate. The inactivation 1) is first order in inhibitor (Kd = 1.9 mM, k2 = 0.05 min-1, pH 5.0), 2) exhibits saturation kinetics, and 3) is dependent on O2 and ascorbate. Restoration of activity could not be achieved by dialysis. The substrate, p-tyramine, protects the enzyme from inactivation, while in initial velocity kinetic experiments, PHBC is a linear competitive inhibitor (Kis = 2.6 mM) versus p-tyramine. The Kis value for PHBC is in good agreement with the Kd value obtained from analysis of the inactivation reaction. PHBC (in the presence of O2 and ascorbate) is also a substrate for the enzyme, being converted to p-hydroxymandelonitrile (PHMN) at a relative Vmax 13% that of p-tyramine. Under these conditions, the ratio of product formation to inactivation is 8000:1, suggesting that PHMN (or a tautomer of PHMN) is the species responsible for inactivation. Indeed, incubation of the enzyme with PHMN in the absence of ascorbate leads to irreversible inactivation. Since PHMN breaks down to p-hydroxybenzaldehyde and cyanide, experiments were conducted to determine whether these compounds may have been responsible for the inactivation. Incubation of the enzyme with p-hydroxybenzaldehyde did not lead to inactivation, whereas the inactivation produced with cyanide could be reversed by dialysis. Thus, the data point to PHMN as the molecule responsible for time-dependent loss of activity of the enzyme. Together, these experiments demonstrate that the newly discovered inhibitor, PHBC, meets the critieria for a suicide substrate for dopamine beta-hydroxylase.

Acetonitriles↗
PubMed1993

Determination of local catecholamine release by microdialysis.

Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in combination with an ultrasensitive radio-enzymatic noradrenaline assay. Experiments were performed in conscious dogs with and without tyramine added to the perfusion medium. In the absence of tyramine, the interstitial noradrenaline levels in subcutaneous tissue were similar to arterial blood concentrations provided the former were corrected for recovery. With tyramine added to the perfusion medium, noradrenaline levels in subcutaneous tissue increased tenfold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. In four healthy males, the subcutaneous dialysate noradrenaline concentration increased during cold exposure by a factor of 3.5 (Friedman test, P < 0.003). Skin temperature decreased by an average of -12 degrees C +/- 0.6 degrees C during cold exposure. The microdialysis technique in combination with a sensitive radio-enzymatic noradrenaline assay may be useful to assess local subcutaneous noradrenaline release.

Adult↗
PubMed1995

Renal catabolism of recombinant human soluble CD4 after intravenous administration to male Sprague-Dawley rats.

Recombinant soluble CD4 (sT4; mol. wt. 45,000) has been studied extensively in Sprague-Dawley rats, and substantial renal processing has been indicated. In rats and monkeys, renal filtration and precipitation of sT4 in the distal nephron caused tubular cast nephropathy. Intravenous pharmacokinetics in the rat demonstrated that sT4 plasma clearance exceeded the glomerular filtration rate. In an effort to determine quantitatively the extent to which kidney and other tissues were responsible for sT4 catabolism, sT4 was labeled with trace amounts of dilactitol-[125I]tyramine and administered intravenously to Sprague-Dawley rats (1 mg/kg). Dilactitol-tyramine accumulates in lysosomes at the site of protein degradation. It has been used primarily to demonstrate hepatic catabolism of endogenous proteins. Blood samples were drawn for pharmacokinetic analysis, and selected tissues were removed to assess radiolabel distribution. Comparison of pharmacokinetic parameters derived from total plasma radiolabel and functional ELISA were not significantly different. Thus, covalent modification of sT4 with dilactitol-tyramine did not appreciably change the rate of clearance. From 3 to 24 hr after intravenous administration, 81.5 +/- 0.1% of the total administered radioactivity was found in the kidney. Approximately 8-13% of the administered dose was recovered in the liver. Macroscopic autoradiography of the kidney demonstrated accumulation of radiolabel in the cortex. Light microscopic autoradiography of the kidney following intravenous administration of directly radioiodinated sT4 confirmed cortical processing, because radiolabel was located primarily in epithelial cells of P1 and P2 segments of the proximal tubule after low intravenous doses (0.4-4 mg/kg). At 40 mg/kg, distal tubules and cortical collecting ducts were labeled as well. Thus, sT4 was filtered by the glomerulus, reabsorbed in the proximal tubule, and degraded in the lysosomal compartment.

Animals↗
PubMed1996

[Digestive amines of bacterial origin and behavior disorders. Apropos of a case].

Implication of amines in central nervous system diseases such as migraine, Parkinson disease, epilepsy and depressive illness, is well established. On an other hand, intestinal flora is responsible for the production of specific metabolites such as amines, particularly histamine, tyramine, putrescine and cadaverine. These amines can be absorbed in situ and, through unknown mechanisms, may affect the host's behavior. Most of the data about the pathological activities of bacterial amines concern animals. The concentrations of histamine, tyramine, putrescine and cadaverine in the feces of the studied "controls" appeared steady over time. For the patient presenting clastic crisis without any starting factor, variations appear to overcome the "controls" values, with a great variability. At least tyramine, putrescine and cadaverine concentrations variations are striking by superposed and seem associated to the arising hyper agressivity crisis.

Adrenergic Agents↗
PubMed1976

Dopamine receptors and dopaminergic nerves in the vas deferens of the rat.

Phentolamine antagonized competitively the effects of noradrenaline (pA2 = 7.1), dopamine (pA2 = 8.0) and tyramine (pA2 = 8.2). Haloperidol had a pA2 value of 7.3 against dopamine and 6.5 against noradrenaline. Apomorphine antagonized competitively dopamine (pA 2 = 4.8) and tyramine (pA2 = 5.1) and noncompetitively antagonized noradrenaline (pD'2 = 3.6). From these data it is concluded that these antagonists interact with dopamine receptors and alpha-adrenergic receptors. Apomorphine (10-4 M) attenuated the maximal response to dopamine and field stimulation, whereas the same concentration of apomorphine potentiated the maximal response to noradrenaline. Assuming that tyramine and field stimulation release the naturally occurring neurohumoral transmitter from adrenergic nerve endings, it is concluded that dopamine is the physiologically functional neurohumoral transmitter in the rat vas deferens which, when released, stimulates specific dopamine receptors.

Animals↗
PubMed1962

An action of 5-hydroxytryptamine on adrenaline receptors.

Contractions of isolated strips of cat spleen due to 5-hydroxytryptamine, adrenaline, histamine and acetylcholine were antagonized by phenoxybenzamine. Responses to both 5-hydroxytryptamine and adrenaline were not blocked in strips which were protected by a high concentration of either 5-hydroxytryptamine or adrenaline throughout exposure to phenoxybenzamine. The contraction due to a large dose of 5-hydroxytryptamine lasted less than 1 hr even when the drug was still present. Strips thus desensitized to 5-hydroxytryptamine responded normally to acetylcholine and histamine but did not respond to adrenaline. The actions of 5-hydroxytryptamine and adrenaline were blocked by 2-bromolysergic acid diethylamide or by dihydroergotamine. These results indicated that 5-hydroxytryptamine and adrenaline act on the same receptors. Cocaine potentiated the action of adrenaline but inhibited the action of 5-hydroxytryptamine. The sensitivity to 5-hydroxytryptamine of spleen strips from cats treated 24 hr earlier with reserpine was only one-fiftieth of that of normal strips. Cocaine potentiated the action of 5-hydroxytryptamine on strips from reserpine-treated cats. A high concentration of 5-hydroxytryptamine in spleen strips from reserpine-treated cats and in cocaine-treated strips prevented phenoxybenzamine from blocking the actions of adrenaline. The effects of tyramine on spleen strips almost exactly paralleled the effects of 5-hydroxytryptamine. Strips showing tachyphylaxis to tyramine did not respond to 5-hydroxytryptamine. It is concluded that 5-hydroxytryptamine has a dual action, viz., a major action due to release of stored noradrenaline and a minor direct action of adrenaline receptors.

Acetylcholine↗