Erkka Solatunturi

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.

Dietary habits affect the susceptibility of low-density lipoprotein to oxidation

Objective: To study, if there are differences in the fatty acid composition of low‐density lipoprotein (LDL) in people eating three different long‐standing habitual diets: vegetarian, high fish intake, or high saturated fat (milk fat) diet as a control group, and to study if these differences influence the oxidation susceptibility of LDL.Design: Cross‐sectional study using blood samples and a validated dietary frequency questionnaire with illustrations.Setting: Helsinki University Central Hospital, Finland.Subjects: The effect of three different types of long‐standing diets of different fatty acid content (a strict vegetarian diet, n=11; a high fish intake diet, n=9; and a high saturated fat (milk fat) diet, controls, n=7) on the serum and LDL fatty acid content, and on the susceptibility of LDL to oxidation in vitro, was studied in healthy normocholesterolemic volunteers who had been on these diets for years. Oxidation of LDL was carried out by using CuSO4 as a pro‐oxidant.Results: There were no statistically significant differences in the serum lipids or lipoproteins, though the vegetarian group exhibited lowest mean values of total, high‐density lipoprotein (HDL) and LDL cholesterol levels. Both the serum and LDL eicosapentaenoic, docosapentaenoic and docosahexaenoic acid proportions were highest in the fish and lowest in the vegetarian groups. Linoleic acid was highest among the vegetarians. In the fish group, the vitamin A concentration in serum was higher than in vegetarians and controls and β-carotene lower than in controls, but in α‐tocopherol, or lycopene concentrations there were no statistically significant differences. The lag phase of LDL oxidation was shortest (116 min) in the fish group and longest (165 min) in the vegetarian group, and the control group was between them (129 min). The mean oxidation percentage after 2.5 h of copper‐induced oxidation was highest (44%) in the fish group and lowest (22%) in the vegetarian group and intermediate (31%) in the control group.Conclusion: Long‐term dietary habits predict the fatty acid composition of serum and LDL, and influence the susceptibility of LDL to oxidation. In the fish group with the highest content of omega‐3 fatty acids in LDL, the oxidation susceptibility of LDL was highest. In the vegetarian group with less omega‐3 fatty acids in LDL, the LDL was more resistant to oxidation.Sponsorship: Helsinki University Central Hospital.

Blood Platelet as a Model for Monoaminergic Neurons

Publisher Summary Platelets contain usually a number of vacuoles of various shapes and dimensions. These organelles can be involved in the phago- and exocytotic activities of platelets. Vacuoles, small vesicles and fine channels seen in platelets, have been theorized as forming a canalicular system with connections to the cell surface. The platelets of man, rabbit, cattle, and dog also exhibit considerable monoamine oxidase (MAO) activity, while this is missing in cat, horse, and rat platelets. Typical of blood platelets is a marginal bundle of microtubules lying along the cell membrane in the equatorial plane of the cell. The diameter of the platelet microtubules is about 20 to 30 nm, and they are composed of about 12 filamentous subunits. These subunits resemble the filaments or microfibrils that are seen in platelets crossing in the cytoplasm. The microfibrils have been suggested to be thrombosthenin—the contractile protein of platelets. Platelet microtubules are labile structures and disappear when platelets become spherical in cold or incubated with rather high concentrations of various agents such as colchicine, vinca alkaloids, and chlorpromazine.

Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro

The present study was aimed to test the possible cyclooxygenase (COX)-1/COX-2 selectivity of the old analgesic drug phenacetin and its metabolite p-phenetidine, which exhibits high renal toxicity. Paracetamol (acetaminophen), the main metabolite of phenacetin with low renal toxicity, and indomethacin were selected as reference compounds. Collagen-stimulated platelet thromboxane B2 (TxB2) production and phorbol 12-myristate-13-acetate (PMA)-induced neutrophil prostaglandin E2 (PGE2) synthesis were used as indicators for COX-1 and COX-2 activity, respectively. Phenacetin was even less potent than paracetamol to reduce the production of both TxB2 and PGE2, and no clear preference for either of the COX-enzymes was seen. P-phenetidine was a more potent inhibitor, already at nanomolar level, of the synthesis of these prostanoids than indomethacin and showed some preference to COX-2 inhibition. Somewhat higher, micromolar, concentrations of p-phenetidine also reduced COX-2 expression in neutrophils. We suggest that the very potent inhibitory activity of p-phenetidine on PGE2 synthesis combined with the reduction of COX-2 expression could explain the renal papillary necrosis in phenacetin kidney.

Subcellular distribution of some phenothiazines in blood platelets of rabbit

Platelets incubated in plasma containing 5 times 10−5 and 3 times 10−4 M chlorpromazine, desmonomethylchlorpromazine or chlorpromazine sulphoxide were homogenized and fractioned by differential centrifugation. After fractionation most of the accumulated chlorpromazine and desmonomethylchlorpromazine were found in the particulate fractions, while most of the chlorpromazine sulphoxide was in the supernatant. The phenothiazines studied had a certain affinity for that fraction containing most of the platelet 5‐hydroxytryptamine (5‐HT). These phenothiazines released half of the platelet 5‐HT without altering its intracellular distribution. The distribution of 5‐HT was affected only by concentrations of chlorpromazine and desmonomethylchlorpromazine which released nearly all of the platelet 5‐HT.

Taurine diet decreases spontaneous and increases exploratory activity of spontaneously hypertensive rats.

Summary Male spontaneously hypertensive Wistar rats (SHR) and normotensive Wistar-Kyoto rats (WKR) were maintained on low taurine (T-) diet and high T (T+) diet (T 3 % in the drinking fluid) and their spontaneous motility and open field exploratory activity were measured at the age of three months. T+ diet decreased the spontaneous motility of the SHR when compared to controls. SHR showed significantly greater open field activity than WKR. This exploratory activity was further enhanced by both T+ and T- diets in the SHR but not in the WKR strain. There were no significant differences between total brain T and 5-HT contents due to the strain or the diet. Taurine rich diet seems to inhibit the spontaneously very intensive activity of the SHR but at the same time to decrease their reactivity to stressful stimuli.

Proliferative effects of oxidized low-density lipoprotein on vascular smooth muscle cells: Role of dietary habits

The effects were studied of native, partially-oxidized and totally-oxidized human low-density lipoprotein (LDL) on the proliferation of cultured rat aortic smooth muscle cells (VSMC), measured as an altered DNA synthesis. The LDL was obtained from three different human long-term diet groups (a control diet rich in saturated fats, a vegetarian diet, and a fish diet). The oxidized LDLs were prepared by oxidizing the LDL with copper sulfate. The DNA synthesis was measured by [3H]-thymidine incorporation into the DNA. The partially-oxidized LDL was the most potent promoter of DNA synthesis compared to the native or totally-oxidized LDL of the same diet group. The partially-oxidized LDL had a true mitogenic effect in the absence of exogenous growth factors. The native and totally-oxidized LDL induced a significant increase in DNA synthesis, if they were obtained from the fish diet group. This study suggests an enhanced proliferative effect of partially-oxidized LDL on VSMC growth.

β-alanine and α-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats

1% β-alanine and α-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). β-Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. α-Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.