[Binding of (3)-imipramine by platelets from spontaneously hypertensive, normotensive, and Wistar rats and their behavior in stressful situations]. / Sviazyvanie (3)-imipramina trombotsitami spontanno gipertenzivnykh, normotenzivnykh i krys linii vistar i ikh povendenie v stress-situatsiiakh.

Spontaneously hypertensive rats (SHR), when submitted to stress remained active during both avoidance (water escape task test) and nonavoidance (forced swimming test) stress-situations. Wistar rats responded to a depression of active behaviour in forced swimming test and difficulty at resolving of complicated problem in water escape task test. did not differ in the affinity but the number of binding sites of 3H-imipramine was greater in SHR. SHR rats had a smaller number of binding sites that Wistar ones.

Taurine in the osmoregulation of the Brattleboro rat.

The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and 3H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

Effect of acetylsalicylic acid on plasma thromboxane B2 and platelet aggregation in man.

The effect of acetylsalicylic acid (ASA) on plasma thromboxane A2 (TXA2) and platelet aggregation was studied in 12 healthy, non-smoking, male students, in a double-blind, cross-over study, after single doses and 14-days on ASA 50, 100, 250 and 1000 mg/day. Platelet production of TXA2 was assessed by measuring the thromboxane B2 (TXB2) content of clotted venous blood by RIA. Platelet aggregation induced by ADP and adrenaline was studied by the method of Born. All doses of ASA completely suppressed the production of TXB2 within 3 h, with the exception of the 50 mg dose, which effected only 61% suppression (p less than 0.001). After administration for 14 days the suppression was complete, even including the lowest dose. At that time ASA had blocked the secondary phase of adrenaline- and ADP-induced platelet aggregation. It is concluded that the maximal antithromboxane and antiaggregatory effects, which last for at least 24 h, can be achieved by continuous daily administration of ASA 50 mg.

Cardiovascular and ventilatory effects of taurine and homotaurine in anaesthetized rats.

The cardiovascular and ventilatory effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) injections of the aminosulphonic acids, taurine and homotaurine, were studied in urethane-anaesthetized rats. Taurine induced dose-dependent falls in blood pressure, heart rate and ventilatory tidal volume on i.c.v. but not on i.v. administration. Homotaurine induced dose-dependent hypotension and bradycardia when given i.v. and i.c.v. It was, however, more effective when injected i.c.v., and the decrease in ventilatory tidal volume occurred after i.c.v. administration of homotaurine only. Pretreatment of the rats with reserpine attenuated both the hypotensive and bradycardic responses to taurine and homotaurine. Atenolol and atropine both partly inhibited, and in combination totally abolished, the bradycardic effects of taurine and homotaurine without changing the hypotensive responses to these compounds. The ventilatory responses were not significantly changed by any of the pretreatments. The results suggest that the central cardiovascular effects of taurine and homotaurine are mediated both by a decrease in sympathetic tone and an increase in the parasympathetic tone.

Taurine in human auricular myocardium and blood platelets.

Blood platelets have been used as a model for the aminergic neurones. In the hypertrophied left ventriles and platelets of spontaneously hypertensive rats the taurine content increases simultaneously. The main purpose of this work was to compare the taurine contents of human platelets and heart tissue. The taurine content was estimated from blood platelets and from the right atrial appendage removed during open heart surgery in 43 patients suffering from ischaemic heart disease. The results indicate that the taurine content increases in the hypertrophied right atrium of the patients with atrial septal defect, as it had previously been shown to increase in the hypertrophied left ventricle in patients who died of congestive heart failure. No correlations were found: 1) between the heart and platelet taurine contents of different groups, 2) between the atrial and platelet taurine in the pooled total results, 3) between the diastolic blood pressure and atrial or platelet taurine levels. Thus the increased taurine content of the auricular tissue is not reflected in the taurine content of the platelets.

beta-Alanine and alpha-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats.

1% beta-alanine and alpha-L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR) but not that of the normotensive Wistar-Kyoto rats (WKR). beta-Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. alpha-Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.

Platelet taurine in patients with arterial hypertension, myocardial failure or infarction.

The content of taurine in the hypertrophied left ventricle is increased in congestive heart failure an in spontaneously hypertensive (SH) rats. In SH rats the taurine content of and taurine uptake by the platelets are also increased. The present results indicate that, as in the heart, the taurine content may also increase in the platelets of those patients with congestive heart failure. The taurine content and uptake are not increased in the platelets of hypertensive patients as they are in the platelets of SH rats. It is likely that in acute myocardial infarction, a considerable amount of taurine is released from the heart into the plasma. However, there is no simultaneous increase in the platelet taurine content. From this work on can only conclude that platelets may reflect taurine changes in the heart in some pathological states, e.g. congestive heart failure.

Platelet taurine in Down's syndrome.

Endogenous platelet taurine and uptake of radioactively labelled taurine by platelets was measured in normal, non-mongoloid and mentally retarded mongoloid trisomy 21 subjects. Endogenous taurine was normal in all groups, while taurine transport kinetic experiments showed normal Km but reduced Vmax in mongoloid trisomy 21 and mentally retarded patients. The latter difference may be due to decreased metabolism following decreased enzyme protein synthesis.

Transport of taurine by normal human blood platelets.

1 Because normal human blood platelets contain higher concentrations of taurine than any other amino acid, and have a platelet: plasma concentration gradient exceeding 400: 1, we isolated the cells in vitro and incubated them with radioactively labelled taurine in order to investigate the existence of a metabolically-dependent accumulation process.2 Platelets incubated with taurine (1 to 100 nmol/ml) in autologous plasma or Krebs solution accumulated [(14)C]-taurine against the concentration gradient.3 The transport process was saturable at high concentrations, showed a requirement for sodium ions, and was temperature-dependent.4 The kinetics of transport fulfilled the criteria of Michaelis & Menten for saturable enzyme/substrate interactions, but the kinetic constants were influenced by the incubation medium.5 The metabolic inhibitors 2,4-dinitrophenol and iodoacetic acid in combination inhibited taurine transport in Krebs solution, but stimulated transport in autologous plasma. The latter result suggested the involvement of a sodium-dependent ATPase in taurine transport.6 We conclude that platelets actively transport taurine in vitro under experimental conditions closely resembling those likely to occur in vivo, and that this taurine transport process may be involved in the maintenance of the platelet: plasma concentration gradient.