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Prostaglandin F2α derivatives as prostaglandin antagonists
PROSTAGLANDINS
Enhancement of the Hyperthermic Effects of SupracorticallyApplied PG's by Systemic Pretreatmentwith Inhibitors of PG Transport or Synthesis Martin C. Wallenstein, Laszlo 2. Bito Research Division, Department of Gpthalmology,College of Physicians and Surgeons, Columbia University, New York, N.Y. 10032 ABSTRACT The effect of supracorticallyapplied PG's on body temperature (BT) was studied in conscious rabbits before and after systemic administrationof inhibitors of PG transport or synthesis. Superfusion of 8 ug of PGEl over the visual cortex of untreated rabbits produced only a small, statisticallynot significant, increase in ET. Within 1 hr but less than 5-6 hr after the systemic administrationof PG transport inhibitors, 200 mg/kg probenecid or 2 mg/kg bromcresol green, which by themselves did not raise and in some cases lowered BT, superfusion of 8 ug of PGEl or PGF a over the cortex produced a statisticallysignificant increase in ST. This effect is assumed to be due to the fact that the supracortically applied PG is not effectively removed by absorptive transport across the blood-brain barrier and this it can reach the subcortical temperature centers more effectively. PGEl also caused significant elevations in BT when superfused over the cortex 2-24 hr after, but not less than 1 hr after, systemic pretreatment with a low dose (10 mg/kg) of indomethacinor paracetamol (50 mg/kg) which can be expected to inhibit PG synthesis but not PG transport. These observations are interpreted to indicate that the sensitivity of the temperature centers to PG was increased, i.e., in the absence of endogenous PG production, there is development of supersensitivity to exogenous PG's. These results indicate that the hyperthermic effects of supracorticallyapplied PG's can be enhanced by systemic pretreatmentwith compounds that can be expected to inhibit the rapid removal of PG's from the brain or lead to the development of supersensitivitydue to elimination of endogenous PG production. In vitro studies indicate that a variety of drugs are effective inmbitors of PG transvort. The effects of such aruss on the removal of PG's from the brain must be considered whether
Enhancement of the Hyperthermic Effects of SupracorticallyApplied PG's by Systemic Pretreatmentwith Inhibitors of PG Transport or Synthesis Martin C. Wallenstein, Laszlo 2. Bito Research Division, Department of Gpthalmology,College of Physicians and Surgeons, Columbia University, New York, N.Y. 10032 ABSTRACT The effect of supracorticallyapplied PG's on body temperature (BT) was studied in conscious rabbits before and after systemic administrationof inhibitors of PG transport or synthesis. Superfusion of 8 ug of PGEl over the visual cortex of untreated rabbits produced only a small, statisticallynot significant, increase in ET. Within 1 hr but less than 5-6 hr after the systemic administrationof PG transport inhibitors, 200 mg/kg probenecid or 2 mg/kg bromcresol green, which by themselves did not raise and in some cases lowered BT, superfusion of 8 ug of PGEl or PGF a over the cortex produced a statisticallysignificant increase in ST. This effect is assumed to be due to the fact that the supracortically applied PG is not effectively removed by absorptive transport across the blood-brain barrier and this it can reach the subcortical temperature centers more effectively. PGEl also caused significant elevations in BT when superfused over the cortex 2-24 hr after, but not less than 1 hr after, systemic pretreatment with a low dose (10 mg/kg) of indomethacinor paracetamol (50 mg/kg) which can be expected to inhibit PG synthesis but not PG transport. These observations are interpreted to indicate that the sensitivity of the temperature centers to PG was increased, i.e., in the absence of endogenous PG production, there is development of supersensitivity to exogenous PG's. These results indicate that the hyperthermic effects of supracorticallyapplied PG's can be enhanced by systemic pretreatmentwith compounds that can be expected to inhibit the rapid removal of PG's from the brain or lead to the development of supersensitivitydue to elimination of endogenous PG production. In vitro studies indicate that a variety of drugs are effective inmbitors of PG transvort. The effects of such aruss on the removal of PG's from the brain must be considered whether