Availability Of Catecholamines Research Articles

Uptake of catecholamines in guinea pig lung: Influence of cortisol and anaphylaxis

Effects of cortisol and anaphylaxis on the uptake of catecholamines (CA) in the guinea pig lung have not been investigated previously. Sensitized and healthy animals were randomly killed, catheters were inserted into the pulmonary artery and vein, and the preparation was perfused with Tyrode. Half of the animals received 50 mg. of cortisol 2 hours before the procedure. H 3-epinephrine (E) or norepinephrine (NE), 10 ng. per milliliter, was infused for 6 minutes. Infusion was started 15 seconds prior to challenge with ovalbumin or NaCl. Total -H 3 and NE(E)-H 3 were determined in the lung homogenates. Results showed (1) 6 to 14 per cent of circulating CA were retained by the lung. (2) In healthy animals cortisol inhibited NE uptake by 35 per cent and E uptake by 15 per cent. (3) Anaphylaxis increased NE and E accumulation by 10 and 19 per cent, respectively. (4) Regardless of experimental conditions approximately 40 per cent of NE and 30 per cent of E taken up were recovered unchanged. In conclusion: (1) There is significant uptake of CA in the lung. (2) One of the mechanisms of therapeutic effect of cortisol in asthma might be its inhibitory effect on CA uptake. (3) Increased CA accumulation during anaphylaxis could be beneficial by increasing the local concentration of amines, or detrimental by decreasing availability of CA, depending on the uptake site and cell type and degree of subsequent metabolism. (4) Cortisol and anaphylaxis per se appear not to change degradation of CA.

Theoretical view of REM sleep function: Maintenance of catecholamine systems in the central nervous system

We hypothesize that rapid eye movements (REM) sleep may play a role in maintaining the functioning of catecholamine-containing neurons in the central nervous system. The main lines of evidence supporting this view are (a) following REM deprivation the responsiveness of catecholamine systems is depressed; (b) administration of drugs which enhance catecholamine activity can reverse some of the behavioral deficits which occur after REM deprivation; and (c) acute administration of pharmacological agents which depress catecholamine activity (alpha methyltyrosine, reserpine) produce a “compensatory≓ increase in REM time whereas increasing central catecholamine availability at the synapse (electroconvulsive shock, imipramine, monoamine oxidase inhibitors) decreases REM sleep. It is suggested that the mechanism of REM is primarily cholinergic and that the locus coeruleus may be the site of interaction between the catecholamine-REM function and the cholinergic-REM mechanism. Evidence is discussed relating to the possibility that REM sleep may have a more general function in the central nervous system, i.e., the modulation of protein synthesis in the brain.

Tissue catecholamines and daily rhythm of liver microsomal enzyme activity

A daily rhythm of liver microsomal enzyme activity and plasma corticosterone levels with a minimum during the light period and a maximum in darkness was found in rats. Treatment with α-methyl-tyrosine consistently increases the plasma corticosterone concentrations and abolishes the fluctuations of microsomal enzyme activity. Intraventricular or intravenous injection of 6-OH-dopamine does not modify the fluctuation of the corticosterone levels nor the enzymatic activity of the microsomes at the different times of the day. The relationship between the brain catecholamine availability and the daily rhythm of drug metabolism is discussed.

Desynchronized sleep deprivation: Learning deficit and its reversal by increased catecholamines

Four days of desynchronized sleep (D) deprivation (island technique) produced a significant deficit in subsequent acquisition of an active avoidance task in the rat. Four days of repeated stress resulting in similar adrenal and thymus changes had no effect on acquisition. L-dopa 200 mg/kg in normals produced a significant deficit in acquisition, but L-dopa after four days of D-deprivation resulted in normal acquisition. (Thus L-dopa reversed the learning deficits produced by D-deprivation, an effect we have shown previously for MAO inhibitors and imipramine.) Alpha-methylparatyrosine also produced a deficit in avoidance acquisition, and L-dopa significantly reduced this deficit, suggesting that the catecholamine increase produced by L-dopa is involved. We suggest that D-deprivation produces defects in the functioning of central catecholaminergic neuronal systems, and that the defects are reversible by increasing the availability of catecholamines.

Effects of lithium and of pH on synaptosomal metabolism of noradrenaline.

CURRENT hypotheses about mania and depression are that they correspond to greater or lesser availability of catecholamines at central synapses1, or to changes in electrolyte and water distribution2. The mode of action of lithium salts, which seem to be effective at least in mania, has been related to both hypotheses3. There are several findings regarding catecholamine metabolism. They include a disappearance of brain noradrenaline after inhibition of tyrosine hydroxylase which is more rapid following Li+ treatment4; a shift in brain metabolism of noradrenaline from extracellular methylation (by catechol-O-methyl transferase), toward intraneuronal deamination (by monoamine oxidase)5; and a decreased rate of release of 3H-noradrenaline during electrical stimulation of brain slices in vitro6. Evidence regarding effects of Li+ on active uptake of noradrenaline into neurones, a major means of inactivation of catecholamine released at synapses, is somewhat in conflict. One study7 reported enhanced uptake in vitro of 3H-noradrenaline into synaptosomes (“pinched-off nerve endings”) prepared after the administration of large amounts of unneutralized Li2CO3. This finding has not been confirmed, and there is evidence that uptake of 3H-noradrenaline into intact brain5, or brain slices6, may not be altered by prior treatment of rats with LiCl. Thus questions arise as to the effect of carbonate ion or pH on amine uptake. These findings, together, suggest that lithium may tend to keep noradrenaline in a pre-synaptic location, while increasing catabolism, particularly by oxidative deamination. The net effect would be decreased availability of this putative transmitter at central synapses, an interpretation consistent with the antimanic effects of lithium.

Discussion of the Effects of Benzoquinolizines and Ring-Substituted Aralkylamines on Serotonin Metabolism

Publisher Summary The biochemistry and pharmacology of synthetic benzoquinolizines and ring-substituted aralkylamines points out two facts, which are pertinent to their mode of action: (1) structurally unrelated drugs, which impair the intraneuronal storage of both indolealkyl and catecholamines, thus increasing the levels of their deaminated metabolites, evoke the typical reserpine like syndrome and (2) inhibitors of monoamine oxidase (MAO) and blockers of the amine-concentrating mechanism in the cell membrane of the adrenergic neuron, such as the tricyclic antidepressants, antagonize and even “reverse” the reserpine like syndrome. The availability of free catecholamines rather than that of indolealkylamines at central effector sites are essential for the antagonism of benzoquinolizines by both MAO inhibitors and tricyclic antidepressants. MAO inhibitors also prevent the depletion of brain monoamines by the reserpinelike benzoquinolizines. This interaction of MAO inhibitors with reserpinelike drugs is described in this chapter.

Possible physiological determinats of a possible dream-intensity cycle

We hypothesize that rapid eye movements (REM) sleep may play a role in maintaining the functioning of catecholamine-containing neurons in the central nervous system. The main lines of evidence supporting this view are (a) following REM deprivation the responsiveness of catecholamine systems is depressed; (b) administration of drugs which enhance catecholamine activity can reverse some of the behavioral deficits which occur after REM deprivation; and (c) acute administration of pharmacological agents which depress catecholamine activity (alpha methyltyrosine, reserpine) produce a “compensatory≓ increase in REM time whereas increasing central catecholamine availability at the synapse (electroconvulsive shock, imipramine, monoamine oxidase inhibitors) decreases REM sleep. It is suggested that the mechanism of REM is primarily cholinergic and that the locus coeruleus may be the site of interaction between the catecholamine-REM function and the cholinergic-REM mechanism. Evidence is discussed relating to the possibility that REM sleep may have a more general function in the central nervous system, i.e., the modulation of protein synthesis in the brain.