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Biomedical subjects

T Simmet

Publications and source records attributed to T Simmet.

67 records · Page 4Linked to original sources
PubMed1985

Modulation of eicosanoid release from anaphylactic guinea-pig heart with 5-benzoyl-a-methyl-2-thiophene acetic acid (tiaprofenic acid).

The effects of infusion of the non-steroidal anti-inflammatory drugs (NSAID), tiaprofenic acid (2.2 micrograms/min or 10.0 micrograms/min) and indomethacin (1.0 microgram/min) on the release of leukotriene (LT) C4-like immunoreactivity, thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha from isolated perfused anaphylactic guinea-pig hearts were investigated. Tiaprofenic acid at both concentrations used significantly inhibited anaphylactic release of TXB2 and 6-keto-PGF1 alpha as did indomethacin (1.0 microgram/min) which was, however, about ten times more potent in this respect. Release of immunoreactive LTC4-like material was not influenced by the lower concentration of tiaprofenic acid used (2.2 micrograms/min), but significantly enhanced by the higher concentration (10.0 micrograms/min). Thus, the effect of tiaprofenic acid on eicosanoid release by the anaphylactic heart is very similar to that of indomethacin without any differential inhibition of TXB2 or 6-keto-PGF1 alpha formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Release and vasoconstrictor effect of leukotriene C-like immunoreactive material in the anaphylactic guinea-pig mesenteric vascular bed.

Antigen challenge of sensitized isolated guinea-pig mesentery perfused under constant pressure resulted in a significant flow reduction, which was paralleled by the release of leukotriene (LT)C4-like immunoreactivity into the perfusates. The lipoxygenase inhibitor quercetin inhibited the release of immunoreactive LTC4 and simultaneously abolished the antigen-induced mesenteric flow reduction. Mesenteric flow reduction was also observed after injection of exogenous LTC4. The results demonstrate that LTC4 is a constrictor of the mesenteric vascular bed and that endogenous LTC4-like immunoreactive material is a mediator of anaphylactic vasoconstriction in the guinea-pig mesentery.

Anaphylaxis↗
PubMed1984

Formation of leukotriene C4-like material by rat brain tissue.

Pieces of rat brain incubated in oxygenated Tyrode solution were stimulated with the divalent cation ionophore A 23187. Incubation media were assayed for leukotriene (LT) C4-like immunoreactivity as well as for prostaglandin (PG) D2, 6-keto-PGF1 alpha and thromboxane (TX) B2 using specific and sensitive radioimmunoassays. Spontaneous release of the cyclooxygenase products but only of trace amounts of LTC4-like immunoreactivity was detected. Stimulation with ionophore A 23187 increased the level of cyclooxygenase products and to a smaller extent the level of LTC4-like immunoreactivity. Inhibition of cyclooxygenase by indomethacin was paralleled by a significantly increased release of LTC4-like material under basal conditions as well as in the presence of ionophore A 23187. On the other hand, the synthesis of LTC4-like material was significantly decreased by the lipoxygenase inhibitors quercetin and nordihydroguaiaretic acid. The presence of LT-like material in rat brain incubates was confirmed by bioassay. The capacity of brain tissue to synthesize LT-like material may be important for cerebral blood flow as well as cellular functions in the central nervous system.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Formation of lipoxygenase and cyclooxygenase metabolites of arachidonic acid by brain tissue.

Rat brain slices released spontaneously and after challenge with A23187 LTC4-like radioimmunoactivity. Total cat brain ischemia followed by short postischemic reperfusion period resulted in the increased release of lipid peroxides and PGE2 but not in LTC4-like substance by brain slices. In lumbar cerebrospinal fluid of patients with completed stroke presence of LTC4-like material was observed.

Animals↗
PubMed1983

Inhibition of B-16 melanoma growth in vitro by prostaglandin D2.

Prostaglandin D2 was found to be a potent inhibitor of B-16 melanoma cell replication in vitro. The inhibition was dose-dependent between 3x10(-9)M and 3x10(-6)M (IC50 approximately 0.3 microM after 6 days). On a molar basis, PGD2 was a better inhibitor than PGA2 or 16, 16-dimethyl-PGE2-methyl ester (di-M-PGE2) and in higher concentrations (10(-6)-10(-7)M), comparable to retinoic acid. In higher concentrations, PGD2 inhibited DNA, RNA and protein synthesis. The B-16 melanoma cell line which we used synthesized arachidonic acid metabolites which comigrated with PGA2, PGD2, PGE2, and PGF2 alpha on a thin layer chromatography system.

Animals↗
PubMed1980

On the relation between contraction and prostaglandin release in rabbit mesenteric blood vessels.

The rabbit superior mesenteric artery and portal vein were used for a study of the effects of noradrenaline, high potassium, angiotensin II and bradykinin on both the contraction development and PG synthesis (PGE2 and PGF2 alpha) in tissue. Noradrenaline induced contractions but no PG release, high potassium evoked contractions and PG release, angiotensin II elicited contractions and PG release in the mesenteric artery but only PG release in the portal vein, and bradykinin initiated PG release and a small decrease in basal tone. The stimulus-evoked PG release was Ca2+-dependent. It is concluded that, at least in some tissues, stimulus-evoked PG release is completely independent from the contractile mechanism. The variable pattern in contractile responses and stimulus-evoked PG release in various tissue may depend on variations of the stimulus-induced accessibility of Ca2+ ions to either phospholipase A2 or the contractile apparatus.

Angiotensin II↗
PubMed1980

Effect of prostaglandins and thromboxane A2 on the contractility of rabbit splenic capsular smooth muscle.

The effect of various prostaglandins (PGs) and a thromboxane A2 (TXA2)-generating system on the contractility of rabbit splenic capsular smooth muscle has been investigated. PGI2 as well as higher concentrations of PGE1 and 5, 6 beta-dihydro-PGI2 inhibit noradrenaline-induced contractions of the smooth muscle preparation. The TXA2-generating system and high concentrations of PGD2, on the other hand, increase the contractions. The results support the concept that the hypothetical PGI2 receptor on the smooth muscle of the rabbit splenic capsule resembles, in its specificity, the PGI2 receptor on platelets.

Animals↗
PubMedDate not supplied

Lipoxygenase products of polyunsaturated fatty acid metabolism in the central nervous system: biosynthesis and putative functions.

Twenty-five years ago prostaglandin (PG) F2 alpha was identified as the first cyclooxygenase-derived metabolite of polyunsaturated fatty acid metabolism in the bovine central nervous system (CNS). On the other hand, 12-hydroxyeicosatetraenoic acid (12-HETE) was the first lipoxygenase product of polyunsaturated fatty acid metabolism to be identified in rat and gerbil brain. For various cyclooxygenase products of arachidonic acid metabolism a substantial body of evidence suggests a mediator role in CNS functions such as in the regulation of local blood flow, in the induction of fever and in the prevention or limitation of seizure activity. By contrast, rather limited information is available on the possible roles of lipoxygenase products of polyunsaturated fatty acid metabolism in the CNS. This review is intended to give a survey on biosynthesis, regional distribution and possible functional importance of HETEs and leukotrienes (LT) in the CNS.

Animals↗