Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part II.

As shown in the first part of this review, well equilibrated neurotransmission in which 5-HT plays a dominant role is important for proper neuromodulation and adjustment of neuronal network elements. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after different forms of exertions, thereby preventing transient dysregulation. Impairment of neuromodulation and neuronal network in the brain with transient dysfunctions or permanent substantial deficits at manifestation of various types of depression results from prevalent impairment of 5-HT neurotransmission and its central interaction with other neurotransmitter systems.

Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part I.

Serotonin (5-HT), one of the evolutionary oldest central neurotransmitters, regulates the most extensive modulatory behavioral system in the brain of vertebrates. 5-HT projections are influenced by extrinsic and intrinsic impulses from different cortical brain areas, which reach Raphe nuclei over feedback loops, containing external and internal body information about planning, evaluation, motivation or excitation. Serotonergic neurotransmission adjusts neuromodulation with consecutive adequate stimulation of the neuronal network.

Influence of exercise on serotonergic neuromodulation in the brain.

Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A receptors (5-HT(2A)R) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved.

Neuroendocrine system and mental function in sedentary and endurance-trained elderly males.

Hypothalamic-pituitary-adrenal (HPAA) and -gonadal (HPGA) axis modification and cognitive impairments have been reported in elderly subjects and related to physical training status. The aim of this study was to investigate if HPAA and HPGA regulation are altered in elderly distance runners (RUN; n = 8; age: 68.9+/-4.

Blood oxygen partial pressure affects plasma prolactin concentration in humans.

Responses of plasma prolactin (PRL) concentration to acute and repeated changes in blood oxygen partial pressure (PO2a) at rest were investigated in two studies (A; B), with special reference to possible effects mediated via serotonin (5-HT) synthesis. In A, nine male subjects inhaled for 105 min gas containing different oxygen fractions for 6 days. Gas concentrations consisted of 14% (A14), 21 % (A21), 40% (A40), 60% (A60) and 80% (A80) O2 mixed with N2 as well as 100% O2 (A100).

Effect of acute and chronic exercise on plasma amino acids and prolactin concentrations and on [3H]ketanserin binding to serotonin2A receptors on human platelets.

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress. In the present study, the influence was investigated of acute endurance exercise and short-term increase in the amount of training on the concentrations of the 5-HT precursor tryptophan (TRP), of prolactin (PRL) and of branched-chain amino acids (BCAA) in the blood, as well as on the binding of [3H]ketanserin to the serotonin-2A (5-HT2A) receptors on platelets.

Hypothalamic-pituitary-adrenal and -gonadal axis function after exercise in sedentary and endurance trained elderly males.

The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPAA) and -gonadal (HPGA) axis responses to post-exercise (30 min at 65% VO2max) combined corticotrophin, luteinizing hormone and thyrotrophin releasing hormone challenge (0.7 microg/ kg body mass) in elderly distance runners (DR; age: 68.9+/-4.

PMN cell counts and phagocytic activity of highly trained athletes depend on training period.

We tested the hypothesis that polymorphonuclear leukocyte (PMN) cell counts and phagocytic activity determined by latex ingestion and superoxide anion production are influenced by different training periods. We investigated long-distance runners before and up to 24 h after a graded exercise test to exhaustion during moderate training (MT) and intense training (IT) and compared them with untrained (control) subjects. Cell counts and phagocytic activity at rest and after exercise did not differ significantly between MT and control.

Influence on myoadenylate deaminase function in rat skeletal muscle after homologous and heterologous immunization with the purified enzyme.

The aim of the study was to shed some light on the possibility of anti-MAD autoantibodies in cases of rhabdomyolysis or microtraumatic muscular damage causing the symptoms of the acquired myoadenylate deaminase deficiency. Therefore a homologous and a heterologous immunization of rats was carried out with myoadenylate deaminase (MAD; EC 3.5.

Sustained noradrenaline sulphate response in long-distance runners and untrained subjects up to 2 h after exhausting exercise.

We investigated the response of plasma and platelet:free catecholamine ([CA]) and sulphated catecholamine ([CA-S]) concentrations after an incremental treadmill test to exhaustion and during recovery. In triathletes (n = 9) plasma and platelet [CA] and [CA-S] were measured before, immediately after and 0.5 and 24 h after exercise.

The effect of maximal exercise on the activity of neutrophil granulocytes in highly trained athletes in a moderate training period.

Leucocyte cell counts and the phagocytic and chemotactic activities of neutrophil granulocytes were investigated in highly endurance-trained long-distance runners (n = 10) and triathletes (n = 10) during a moderate training period and compared with untrained subjects (n = 10) before and up to 24 h after a graded exercise to exhaustion on a treadmill. After exercise a leucocytosis was noted with a significant increase in lymphocyte (P < or = 0.01) and neutrophil (P < or = 0.

O-Methylated and sulfoconjugated catecholamines: differential activities at human platelet alpha 2-adrenoceptors.

The physiological effects of the sulfoconjugates of epinephrine, norepinephrine, and the 3-O-methylated catecholamines, metanephrine, normetanephrine, and methoxytyramine were examined with regard to their alpha 2-adrenoceptor binding properties and aggregation activity in human platelets. Sulfoconjugation of catecholamines resulted in the loss of both their competitive potency for [3H]yohimbine binding and their influence on platelet aggregation. O-Methyl substituted catecholamines showed attenuation of their alpha 2-adrenoceptor binding affinities when compared with those of the corresponding non-esterified amines.

Interaction between hormones and the immune system.

After a short introduction into the general topic, the catecholamine-induced increase of leukocytes in which the granulocytes are predominant after short-term exercise is discussed. The reduction of lymphocytes is associated with work-dependent cortisol increase after long-term exercise or 1 h after strenous work. The catecholamine-stimulated lymphocytes increase could be explained by the liberation of the cells from the endothelial vessel wall after catecholamine interaction with the beta-adrenoceptors and by mobilization from lymph nodes and spleen after beta-adrenergic stimulation.

Sympathetic neuronal activity in diabetic and non-diabetic subjects with peripheral arterial occlusive disease.

Despite the vasoconstrictory influence of the alpha-adrenergic system on the peripheral blood circulation the results of the sympathectomy were not satisfying in the therapy of peripheral arterial occlusive disease (PAOD). The aim of the present investigation was to clarify the pathophysiologic mechanisms of this clinical observation. Free and sulfoconjugated catecholamines were determined in the femoral artery, vein, and cubital vein of 19 healthy controls, 21 non-diabetic patients with PAOD stage II, 8 non-diabetic (PAOD IV) and 20 diabetic patients (D IV) with PAOD stage IV.

Catecholamine sulfates as internal standards in HPLC determinations of sulfoconjugated catecholamines in plasma and urine.

A method is described to measure catecholamine sulfates from human plasma and urine by isocratic reversed-phase high-performance liquid chromatography with electrochemical detection. For this measurement we use catecholamine 3-sulfate isomers as internal standards and determine the sulfoconjugates only after eliminating the catecholamines. Catecholamines that have previously been used as internal standards are shown to cause a significant overestimation (P less than 0.

Purine nucleotides and AMP deamination during maximal and endurance swimming exercise in heart and skeletal muscle of rats.

The purine nucleotides, phosphocreatine (PCr), ammonia, and lactic acid were investigated in skeletal muscles of rats with prominent type I, type IIa, type IIb fibers, and the heart after exhaustive and endurance swimming tests. ATP, ADP, AMP, IMP, and PCr were determined by HPLC with UV detection in controls after maximal and endurance training for 6 weeks with or without a respective final test and also after final exhaustive or endurance test without preceding training. The swimming time in these tests was longer with than without training.

Blood ammonia determination in a specific field test as a method supporting talent selection in runners.

Twenty-six male runners aged 14-16 years not yet specifically trained for sprint or middle-distance running performed a field test with distances of 25 m, 75 m, and 1000 m. Before the field test they were designated as sprinters (n = 19) and middle-distance runners (n = 7) according to their self-assessment and the estimation of the coaches. Blood ammonia and lactate concentrations were measured before and after the runs, and heart rates as well as the perceived exertion were evaluated.

Comparison of alanine production after L-leucine and AMP deamination in an enzymatic model and in muscle specimens.

The amination of 2-oxoglutarate to glutamate by the deamination of leucine followed by the transamination of pyruvate to alanine in skeletal muscle is generally accepted. However, alanine formation following AMP deamination by AMP deaminase is still questionable even though it is theoretically possible. For this reason, we investigated in an enzymatic model the dependence of alanine yield both on the increasing concentration of AMP and leucine as amino group donors as well as on AMP deaminase and leucine dehydrogenase augmentation.

Sympathoadrenergic regulation and the adrenoceptor system.

We investigated the effects of endurance and high-intensity training periods on the plasma catecholamine (CA) concentration at rest; on the basal alpha- and beta-adrenoceptor density, regulation, and function on circulating cells; and on the cardiovascular adaptation in long-distance runners and swimmers. The findings of each period were compared with those of untrained men. Endurance training of the long-distance runners and the swimmers led both to a reduced sympathetic activity at rest, indicated by lower CA values, and to a lower beta-receptor density and responsiveness on circulating lymphocytes and an increased alpha 2-receptor sensitivity on circulating platelets.

Controlled-release levodopa/benserazide (Madopar HBS): clinical observations and levodopa and dopamine plasma concentrations in fluctuating parkinsonian patients.

In five levodopa (L-dopa)-treated patients with Parkinson's disease with severe fluctuations of motor performance, plasma L-dopa as well as dopamine levels were measured during 2 days, first under optimal standard L-dopa with peripheral decarboxylase inhibitor (PDI) and then after a dose adjustment period using slow-release L-dopa/benserazide (Madopar HBS) in an open inpatient trial. Three patients benefited from the slow-release preparation; two patients deteriorated with a tendency to have an unpredictable response, a delay to turn "on" with the first dose in the morning, as well as an increase in dyskinesia corresponding to L-dopa cumulation during the day. These problems were subsequently also seen during the follow-up period of 1 year in those patients who benefited from Madopar HBS as inpatients.

Isomer specific kinetics of dopamine beta-hydroxylase and arylsulfatase towards catecholamine sulfates.

Both isomers of epinephrine sulfate were synthesized, unequivocally identified by 1H-NMR and highly purified from catecholamines (less than 90 ppm). Bacterial as well as pig liver arylsulfatase A and B demonstrated a higher substrate turnover of epinephrine-4-sulfate, norepinephrine-4-sulfate and dopamine-4-sulfate as compared to the 3-sulfate isomers. The arylsulfatase B however, is less important for the deconjugation of these sulfoconjugates than arylsulfatase A.

Decrease in rat cardiac beta 1- and beta 2-adrenoceptors by training and endurance exercise.

The cardiac beta-adrenoceptor adaptation to physical activity was investigated in rats which were subjected to a six-week endurance swimming training (ET; n = 7) and a training of high intensity (MT; n = 7). In addition, the effect of a single bout of endurance exercise without preceding training (EE; n = 7) was evaluated. These groups were compared with a sedentary control group (C; n = 9).

Assessment of muscular metabolism in peripheral arterial occlusive disease using 31P nuclear magnetic resonance spectroscopy. Comparison with metabolite concentrations in femoral blood.

The behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum ergometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of 31P magnetic resonance spectroscopy and compared with those from a control group. In addition, arteriovenous differences in concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood were determined.