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Biomedical subjects

T Puustinen

Publications and source records attributed to T Puustinen.

31 records · Page 2Linked to original sources
PubMed1984

Albumin stimulates the release of arachidonic acid from phosphatidylcholine in hamster lungs.

14C-Arachidonic acid injected into the pulmonary circulation of isolated hamster lungs was effectively incorporated into lung lipids. Once retained the radiolabel was relatively stable but the release of radioactivity increased up to 10-fold when bovine serum albumin (1%) was added to the perfusate. This efflux of radioactivity was not blocked by quinacrine, a phospholipase A2 inhibitor. In albumin experiments the released 14C-arachidonate originated mainly from the phospholipid fraction in which phosphatidylcholine was the main source of the released radioactivity. Pulmonary infusion of albumin had no significant effect on the amount of 14C-arachidonic acid in the neutral lipid or free fatty acid fractions of perfused lungs. In experiments with albumin about 80% of the released radioactivity co-chromatographed with unlabelled arachidonic acid whereas in the absence of albumin only about 20% of the released radioactivity was unmetabolized arachidonic acid. This study indicates that albumin stimulates the release of arachidonic acid from isolated hamster lungs and that the release is increased mainly from the phosphatidylcholine fraction.

Animals↗
PubMed1984

Thromboxane formation in human polymorphonuclear leukocytes is inhibited by prednisolone and stimulated by leukotrienes B4, C4, D4 and histamine.

Human polymorphonuclear leukocytes (PMNL) were incubated for 60 min at 37 degrees C with 20 microM or 100 microM prednisolone, and stimulated thereafter for 1 min with 10 nM LTB4, 10 nM LTC4, 10 nM LTD4 or 10 microM histamine. The amount of thromboxane B2 (TXB2) formed by PMNLs was measured by radioimmunoassay. PMNLs spontaneously released TXB2 during 60 min incubation, and the rate of formation was significantly reduced in the presence of 20 microM or 100 microM prednisolone. LTB4, LTC4, LTD4, and histamine stimulated the rate of TXB2 production during 1 min incubation to 93-, 49-, 60-, and 55-fold, respectively. Preincubation with prednisolone for 60 min had a slight inhibitory effect on the stimulated TXB2 formation but TXB2 production still remained many fold as compared to its spontaneous rate of formation. The present study indicates that human PMNLs are capable of synthetizing TXB2, and its spontaneous rate of formation is inhibited by a synthetic glucocorticoid, prednisolone. The great stimulatory effect of LTB4, LTC4, LTD4, and histamine suggests that these agents may activate phospholipases or other acylhydrolases which liberate arachidonate for eicosanoid biosynthesis.

Histamine↗
PubMed1984

U-60,257 has no effect on the metabolism of arachidonic acid in nonstimulated human polymorphonuclear leukocytes.

When human polymorphonuclear leukocytes (PMNL) were incubated with exogenous 14C-arachidonic acid only traces of 5-lipoxygenase products including 5-HETE and leukotriene B4 were detected. On the other hand, considerable amounts of cyclo-oxygenase metabolites including PGE2, TXB2, HHT, PGD2, PGF2 alpha and 6-keto-PGF1 alpha as well as mono-HETE's migrating in the vicinity of 12-HETE were formed. Coincubation of PMNL with platelets did not lead to any detectable activation of the 5-lipoxygenase pathway. 10 microM U-60,257, an inhibitor of leukotriene synthesis, had no effect on the low basal 5-lipoxygenase activity nor on other lipoxygenases in either PMNL or during coincubation of PMNL with platelets. The formation of cyclo-oxygenase products was neither affected by U-60,257. It also failed to have any effect on the aggregation of PMNL induced by arachidonic acid, leukotriene B4 or platelet activating factor. The present study indicates that U-60,257, which has been reported to be a specific inhibitor of leukotriene synthesis, has no effect on the cyclo-oxygenase or on lipoxygenases other than the 5-lipoxygenase (i.e. 12- and possibly 15-) in human PMNL and obviously neither in human platelets.

Arachidonate Lipoxygenases↗
PubMed1984

Nicotine has no effect on the metabolism of exogenous arachidonic acid or prostaglandin E2 in isolated perfused rat and hamster lungs.

14C-labelled arachidonic acid and prostaglandin E2 (PGE2) were infused into the pulmonary circulation of isolated rat and hamster lungs, and the radioactive metabolites were analysed from the nonrecirculating perfusion effluent by thin-layer chromatography. Pulmonary infusion of nicotine (1 or 10 microM for 5 min) did not interfere with the metabolite pattern of arachidonic acid or the metabolism of PGE2 by 15-hydroxyprostaglandin dehydrogenase. Nicotine seems not to be responsible for the previously reported cigarette smoke-induced alterations in the pulmonary metabolism of exogenous arachidonic acid and PGE2.

Animals↗
PubMed1983

The distribution of 14C-arachidonic acid in hamster lungs is sensitive to quinacrine.

Isolated hamster lungs were labelled with 14C-arachidonic acid. When the lungs were ventilated with a respirator only a small amount of radioactivity was released to the perfusion effluent. This release was not changed significantly by pulmonary infusion of quinacrine (0.5 mM), a known inhibitor of phospholipase A2. After the perfusion about 75% of the radioactivity in the lungs was in phospholipids, mainly in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol and to a lesser degree in phosphatidylserine and phosphatidic acid. About one fourth of the radioactivity was in neutral lipids (tri- and diacylglycerols) and as free unmetabolized 14C-arachidonic acid. Pulmonary infusion of quinacrine increased the amount of radioactivity in diacylglycerols and phosphatidylinositol but had no effect on that in phosphatidylcholine, phosphatidylserine, phosphatidic acid and triacylglycerols. The amount of radioactivity in phosphatidylethanolamine was decreased by quinacrine and increased in the vicinity of an unidentified phospholipid-quinacrine complex. The present study indicates that the distribution of 14C-arachidonic acid in hamster lung lipids is sensitive to quinacrine. The detected changes can, however, not be explained by an overall inhibition of phospholipase A2 activities.

Animals↗
PubMed1983

The amount of arachidonic acid in the triacylglycerols of perfused hamster lungs is increased by prednisolone.

Following the injection of 14C-arachidonic acid (4.1 nmol) into hamster isolated lungs about 80% of the administered radioactivity was retained by the lungs. During subsequent perfusion only a small amount of radioactivity was released to the perfusion effluent. This release was not affected by pulmonary infusion of prednisolone at 20 microM or 100 microM. In control lungs 84 +/- 1% (+/- SEM) of the retained radioactivity was recovered in the phospholipid, 13 +/- 1% in the neutral lipid and 3 +/- 1 in the free fatty acid fraction. Pulmonary infusion of prednisolone increased the amount of radiolabel in the neutral lipids. This was due to the increased amount of 14C-arachidonic acid in triacylglycerols. Prednisolone had no significant effects on the amount of 14C-arachidonate in diacylglycerols or in different phospholipids. Neither was the amount of free 14C-arachidonate in the lungs changed by prednisolone. The present study indicates that the release of arachidonic acid from triacylglycerols may be inhibited by prednisolone in hamster lungs.

Animals↗
PubMed1983

Dipyridamole interferes with the incorporation of arachidonic acid and stimulates prostacyclin production in rat lungs.

Following the injection of 4 nmol of 14C-arachidonic acid into the pulmonary circulation of rat isolated lungs more than 90% of the radioactivity was retained by the lung tissue. When dipyridamole (20 microM) was infused into the pulmonary circulation during 14C-arachidonate injection the amount of radiolabel was increased in diacylglycerols as well as in phosphatidylinositol and phosphatidylserine of the perfused lungs whereas the amount of radioactivity was decreased in phosphatidylethanolamine. When dipyridamole was infused into the lungs prelabelled with 14C-arachidonic acid the distribution of radiolabel in different lung lipid fractions was not changed significantly. However, dipyridamole seemed to stimulate the formation of prostacyclin in rat lungs as the amount of 6-keto-PGF1 alpha was increased in the perfusion effluent. The present study indicates that dipyridamole interferes with the incorporation of arachidonic acid into different lipids in rat lungs. In addition, the release of prostacyclin seems to be stimulated by dipyridamole.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

The effect of bradykinin, histamine, and leukotrienes B4, C4 and D4 on the formation of 6-keto-prostaglandin F1 alpha and thromboxane B2 in hamster lungs.

Bradykinin, histamine, leukotriene B4, C4, D4 (LTB4, LTC4, LTD4), and bradykinin + LTC4 were injected as a bolus into the pulmonary circulation of hamster isolated lungs, and the amounts of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) in the perfusion effluent were determined by radioimmunoassay. LTD4, bradykinin, and bradykinin + LTC4 stimulated 6-keto-PGF1 alpha formation whereas TXB2 formation was stimulated only by LTB4 and histamine. The detected changes in the activation of arachidonate metabolism were, however, relatively small. The present study indicates that bradykinin, histamine, LTB4, and LTD4 have only a minor stimulating effect on arachidonic acid metabolism in hamster lungs.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Sodium salicylate interferes with the inhibitory effects of aspirin and indomethacin on human platelets.

The interference of sodium salicylate with the effects of acetylsalicylic acid (ASA, aspirin) and indomethacin on arachidonic acid-induced platelet aggregation and thromboxane formation was studied in human platelet rich plasma. ASA and indomethacin suppressed both aggregation and the concomitant formation of thromboxane B2 whereas sodium salicylate alone had no significant effect on these parameters of platelet function. It did, however, partially prevent the inhibitory effects of ASA and indomethacin on platelet aggregation when it was added to platelet rich plasma before ASA or indomethacin. The inhibition of thromboxane formation by indomethacin was also prevented by sodium salicylate. When sodium salicylate was added to platelet rich plasma after ASA or indomethacin it did not modify the effects of these drugs. The present study indicates that sodium salicylate interferes with the effects of ASA and indomethacin on human platelet cyclo-oxygenase in vitro.

Adult↗
PubMed1983

The effects of aspirin and dipyridamole on the metabolism of arachidonic acid in human platelets.

The effects of aspirin and dipyridamole on the metabolism of exogenous 14C-arachidonic acid were investigated in intact human platelets in vitro. The formation of thromboxane B2 (TXB2) and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was inhibited dose dependently by aspirin but not by dipyridamole. Neither was the aspirin caused inhibition in TXB2 and HHT formation modified by dipyridamole. At high concentrations aspirin caused a slight increase in the amount of 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) and a corresponding decrease in that of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). This was seen also when aspirin was combined with dipyridamole. At high concentrations (100 microM and 1 mM) dipyridamole caused an increased formation of 12-HETE and an unidentified metabolite group. The present study indicates that dipyridamole has no effect on the formation of the cyclo-oxygenase metabolites in human platelets but the lipoxygenase pathway seems to be stimulated by dipyridamole.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1982

The effect of hydrocortisone on the metabolism of PGE2 in rat lungs.

Hydrocortisone pretreatment of male rats daily for five days (2 or 10 mg/kg, s.c.) had no significant effect on the total inactivation of prostaglandin E2 in isolated perfused rat lungs or on the activity of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase in the 100.000 x g supernatant fraction of homogenized lungs. Nor did pulmonary infusion of hydrocortisone (0.1 or 1 microM in the perfusion medium) have any effect on the metabolism of PGE2 in isolated rat lungs. The present study indicates that pulmonary inactivation of PGE2 is not changed by hydrocortisone in rat lungs.

Animals↗
PubMed1982

The effect of arachidonic acid on the aggregability of human platelet rich plasma.

Addition of arachidonic acid to human platelet rich plasma caused a reversible aggregation, which was greatly decreased after aspirin ingestion. ADP induced a greater aggregation, which was only slightly decreased after aspirin ingestion. When PRP was incubated with arachidonic acid for 2 or 6 min before the addition of ADP, the ADP-induced aggregation was greatly decreased. This decrease was not changed by aspirin ingestion. The present study indicates that arachidonic acid is metabolized in human platelets not only to aggregatory compounds but also to anti-aggregatory compound(s). The formation of the latter compound is not inhibited by aspirin.

Adenosine Diphosphate↗