- Email: [email protected]
Radioimmunoassay of 13, 14-dihydro-15-keto-prostaglandin F2a
ABSTRACTS PLASMA PROSTAGLANDIN METABOLITES IN HUMAN LABOR. R Laekritz, D Tulehinsky, KJ Ryan, L Levlne. Am. J. Obstet. Gynecol. 131: 484-489, 1978.
ANAPHYLACTIC RELEASE OF HISTAMINE AND SLOW REACTING SUBSTANCE OF ANAPHYLAXIS(SRS-A) FROM GUINEA-PIG LUNG AND ITS MODULATION BY PROSTAGLANDINS. S Kitamura, Y Ishihara, Y Hattori. Jap J Med 17: 3, 1978.
The concentrations of 13,14-dihydro-15-keto-PGE2 and 13,14-dlhydro-15-keto-PGF2~ in pregnant patients at term not in labor were not significantly different from those at midpregnancy. Induction of labor at term pregnancy caused a significant rise of both PGE2-M and PGF2e-M. During spontaneous labor there were no significant minute-to-minute fluctuations of plasma PGE2-M or PGF2~-M and their concentrations were netdifferent from those at oxytocln-induced labor. Initiation of uterine contractions and abortion at midpregnancy by the intraamniotic infusion of hypertonie saline was not associated with any change in PGE2-M concentration and a rise in PGF2~-M was noted in only one of five patients. The vaginal administration of PGE 2 and the intra-amniotic infusion of PGF2~ were associated in each case with a significant rise of both prostaglandln metabolites.
The regulatory mechanism of anaphylactic release of histamine and SRS-A from passlvely sensitized gulnea-pig lung tissues was studled. The release of histamine and SRS-A from sensitized lung tissue was markedly decreased by preincubating with isoproterenol, aminophylline, cyclic AMP.Na and prostaglandln E 2 (PGE2). While the release of both chemical mediators was increased by preincubating wlth cyclic GMP.Na and PGF2G, and by preincubating with the mixture of PGE 2 and PGF2~(I:9), the release of b o t h chemical mediators was markedly increased comparlng with that by preincubating w i t h PGF2~ alone.
STIMULATION OF PROSTAGLANDIN PRODUCTION IN BONE BY PHORBOL DIESTERS AND MELITTIN. AH Tashjlan, Jr., JL Ivey, B Delclos, L Levine. Prostaglandins 16: 221232, 1978.
MODIFICATION OF BIOLOGICAL MEMBRANES PERMEABILITy : A POSSIBLE MODE OF ACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAID). JP Famaey, J Fontaine. Acts Clin Bslg 32: 235,1977
The tumor promoter 12-0-tetradeeanoyl-phorbol-13-acetate (TPA) stimulated PGE 2 synthesis in bone and also bone resorption. The effects of TPA on the production of PGE 2 and bone resorption were inhibited completely by indomethacin (5.6 X 10-8 to 5.6 X 10-7 M). The bee venom toxin, melittln, was also a potent stimulator of prostaglandin synthesis in bone and bone resorption. The effects of melittin on the production of PGE 2 and bone resorption were also inhibited by indomethacin. We conclude that phorbol diestsrs, which have irritant and tumor-promoting activity in mouse skin, and the polypeptide melittln can act directly on bone to stimulate resorption by a mechanism involving the local production of PGE 2 or possibly other indomethacin-lnhihited metabolites of arachldonic acid.
NSAID uncouple mltochondrial oxidative phosphorylatlon and induce an ionodepsndent mitochondrial swelling and an intramltochondrial alkalinization. In lymphocytes they induce an ionodependent swelling and changes in ionic captations. Thls might be due to modifications of membranes permeabillty. This membrane action could explain some of the NSAID effects on the guinea-pig isolated ileum(GPil): inhibitions of contractions induced by electrical coaxial stimulations and of contractions to acstylchollne~ histamine and nicotlne. These are reversed by PG through non-selective ileal sensitlzatlon. Colchicine and vinblastine which stimulate PG synthesls,also increase GPil contractions.
RADIOIMMUNOASSAY OF MAIN URINARY METABOLITE OF PROSTAGLANDIN F2~ IN NORMAL SUBJECTS. S Kitamura, Y Ishihara, K Kosaka. Prostaglandins 14: 961, 1977.
M O D U L A T I O N B Y P R O S T A G L A N D I N S O P THE R E L E A S E O P A C E T Y L C H O L I N E A N D N O R A D R E N A L I N E IN G U I N E A IG I S O L A T E D ILEUM, 0 Kadlec, K Na~ek, I~ eferna. J P h a r m a c o l exp T h e r 205:635,1978.
Radioimmunoassay of 5~,7~-dihydroxy-ll-ketotetranorprosta-l,16-diolc acid, main urinary metabolite of prostaglandin F2~(PGF2~-MUM), was peEformed in normal subjects. Twenty-four hours excretion of P G F 2 ~ - M U M were 29.0~9.7~g in males and 18.2~5.9~g in females, and there was no significant difference between day and night. And there was also no correlation between 24hr urine volume and 24hr excretion of PGF2~-MUM. An oral administration of aspirin( 1.98g) resulted in the significant decrease of PGF2~-MUM. Mean values of 24hr excretion of PG F2~-MUM by rectal suppository of PGF2~(400~g) in male and female volunteers were 103.8~30.1 /ag and [email protected]/g, respectively.
Prostaglandin-like substances released from the i l e u m w e r e mairLly of the E type a n d their output partially correlated with cont r a c t i o n s a n d w i t h the o u t p u t of ACh. The output of ACh, b o t h r e s t i n g a n d stimulated, w a s d e c r e a s e d b y i n d o m e t h a c i n (I ~ ) and i n c r e a s e d b y P G E ~ (6 n~A) but not By PGP~,~ T h i s i n c r e a s e w a ~ i n v e r s e l y r e l a t e d to ~ the initial l e v e l of A C h output. The s t i m u l a t e d (5 Hz) o u t f l o w of N A w a s i n c r e a s e d by i n d o m e t h a c i n (50 /uM) a n d d e c r e a s e d b y P G E 2 (30 nM). T h e s e r e § u l t s s u g g e s t e d that PGEo might p h y s i o l o g i c a l l y m o d u l a t e c h o l i n e r g i ~ transmission whereas adrenergic transmission could be a f f e c t e d only p h a r m a c o l o g i c a l l y .
~
RADIOIMMUNOASSAY OF 13, 14-DIHYDRO-15-KETOPROSTAGLANOIN Fo=. E Youssefnsjadian, H Brodovcky, M Jo~Mson and I Craft.
STIMULATION OF PROBTAGLANDIN SYNTHESIS BY TUMOR-PROMOTING PHORBOL-12,13-DIESTERS IN CANINE KIDNEY (MDCK) CELLS. K. 0huchi, L Levine. J. Biol. Chem. 253: 47834790, 1978.
Department of Biochemical Endocrinology and Institute of Obstetrics and Gynaseology, Chelsea Hospital for Women, London SW3
Tumor-promoting 12-O-tetradecanoyl-phorbol-13-aeetate and phsrbol-12,13-di-decanoate, but not the non-tumor promoting 4~-phorbol-12,13-di-decanoate, stimulated deacylation of cellular llpids, prostaglandin hiosynthesis, and morphological changes in cultured MDCK cells. The increased prostaglandin biosynthesis and morphological changes required at least 24 hrs for expression. Cycloheximide inhibited the stimulated prostaglandin biosynthesis, the changes in morphology and the increased lipid deacylation. Indomsthacin (0.5 pg/ml) completely inhibited the stimulated prostaglandin biosynthesis and also inhibited some deaeylation of cellular lipids. Indomethacin, however, did not affect the 12-0-tetradeeanoyl-phorbol-13-acetatestimulated changes in morphology.
A simple method is descrlbed for the dsterminatlon of 13, 14-dihydro-15-keto-prostaglandin F2a(PGFM), using a highly specific antiserum ralssd in New Zealand rabbits. It involves extraction of human peripheral venous plasma with diethyl ether after addition of tritiated PGFM and HC1. Radioimmunoassay is performed on appropriate aliquots; aftsr 2 hours or overnight equilibration the bound and free metabol i t t e r s separated using dextran-coated charcoal. The mean values + S.D. obtained ars as follows: hsalthy males 32 ± 16 pg/ml, fsmalss during follicular phass 48 + 18 pg/ml, luteal phase 37 + 8 pg/ml, first t~imestsr of pregnancy 66 ~ 33 pg/ml, second trimester 67 ± 42 pg/ml and third trimester 72 ± 26 pg/ml. 81
ANAPHYLACTIC RELEASE OF HISTAMINE AND SLOW REACTING SUBSTANCE OF ANAPHYLAXIS(SRS-A) FROM GUINEA-PIG LUNG AND ITS MODULATION BY PROSTAGLANDINS. S Kitamura, Y Ishihara, Y Hattori. Jap J Med 17: 3, 1978.
The concentrations of 13,14-dihydro-15-keto-PGE2 and 13,14-dlhydro-15-keto-PGF2~ in pregnant patients at term not in labor were not significantly different from those at midpregnancy. Induction of labor at term pregnancy caused a significant rise of both PGE2-M and PGF2e-M. During spontaneous labor there were no significant minute-to-minute fluctuations of plasma PGE2-M or PGF2~-M and their concentrations were netdifferent from those at oxytocln-induced labor. Initiation of uterine contractions and abortion at midpregnancy by the intraamniotic infusion of hypertonie saline was not associated with any change in PGE2-M concentration and a rise in PGF2~-M was noted in only one of five patients. The vaginal administration of PGE 2 and the intra-amniotic infusion of PGF2~ were associated in each case with a significant rise of both prostaglandln metabolites.
The regulatory mechanism of anaphylactic release of histamine and SRS-A from passlvely sensitized gulnea-pig lung tissues was studled. The release of histamine and SRS-A from sensitized lung tissue was markedly decreased by preincubating with isoproterenol, aminophylline, cyclic AMP.Na and prostaglandln E 2 (PGE2). While the release of both chemical mediators was increased by preincubating wlth cyclic GMP.Na and PGF2G, and by preincubating with the mixture of PGE 2 and PGF2~(I:9), the release of b o t h chemical mediators was markedly increased comparlng with that by preincubating w i t h PGF2~ alone.
STIMULATION OF PROSTAGLANDIN PRODUCTION IN BONE BY PHORBOL DIESTERS AND MELITTIN. AH Tashjlan, Jr., JL Ivey, B Delclos, L Levine. Prostaglandins 16: 221232, 1978.
MODIFICATION OF BIOLOGICAL MEMBRANES PERMEABILITy : A POSSIBLE MODE OF ACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAID). JP Famaey, J Fontaine. Acts Clin Bslg 32: 235,1977
The tumor promoter 12-0-tetradeeanoyl-phorbol-13-acetate (TPA) stimulated PGE 2 synthesis in bone and also bone resorption. The effects of TPA on the production of PGE 2 and bone resorption were inhibited completely by indomethacin (5.6 X 10-8 to 5.6 X 10-7 M). The bee venom toxin, melittln, was also a potent stimulator of prostaglandin synthesis in bone and bone resorption. The effects of melittin on the production of PGE 2 and bone resorption were also inhibited by indomethacin. We conclude that phorbol diestsrs, which have irritant and tumor-promoting activity in mouse skin, and the polypeptide melittln can act directly on bone to stimulate resorption by a mechanism involving the local production of PGE 2 or possibly other indomethacin-lnhihited metabolites of arachldonic acid.
NSAID uncouple mltochondrial oxidative phosphorylatlon and induce an ionodepsndent mitochondrial swelling and an intramltochondrial alkalinization. In lymphocytes they induce an ionodependent swelling and changes in ionic captations. Thls might be due to modifications of membranes permeabillty. This membrane action could explain some of the NSAID effects on the guinea-pig isolated ileum(GPil): inhibitions of contractions induced by electrical coaxial stimulations and of contractions to acstylchollne~ histamine and nicotlne. These are reversed by PG through non-selective ileal sensitlzatlon. Colchicine and vinblastine which stimulate PG synthesls,also increase GPil contractions.
RADIOIMMUNOASSAY OF MAIN URINARY METABOLITE OF PROSTAGLANDIN F2~ IN NORMAL SUBJECTS. S Kitamura, Y Ishihara, K Kosaka. Prostaglandins 14: 961, 1977.
M O D U L A T I O N B Y P R O S T A G L A N D I N S O P THE R E L E A S E O P A C E T Y L C H O L I N E A N D N O R A D R E N A L I N E IN G U I N E A IG I S O L A T E D ILEUM, 0 Kadlec, K Na~ek, I~ eferna. J P h a r m a c o l exp T h e r 205:635,1978.
Radioimmunoassay of 5~,7~-dihydroxy-ll-ketotetranorprosta-l,16-diolc acid, main urinary metabolite of prostaglandin F2~(PGF2~-MUM), was peEformed in normal subjects. Twenty-four hours excretion of P G F 2 ~ - M U M were 29.0~9.7~g in males and 18.2~5.9~g in females, and there was no significant difference between day and night. And there was also no correlation between 24hr urine volume and 24hr excretion of PGF2~-MUM. An oral administration of aspirin( 1.98g) resulted in the significant decrease of PGF2~-MUM. Mean values of 24hr excretion of PG F2~-MUM by rectal suppository of PGF2~(400~g) in male and female volunteers were 103.8~30.1 /ag and [email protected]/g, respectively.
Prostaglandin-like substances released from the i l e u m w e r e mairLly of the E type a n d their output partially correlated with cont r a c t i o n s a n d w i t h the o u t p u t of ACh. The output of ACh, b o t h r e s t i n g a n d stimulated, w a s d e c r e a s e d b y i n d o m e t h a c i n (I ~ ) and i n c r e a s e d b y P G E ~ (6 n~A) but not By PGP~,~ T h i s i n c r e a s e w a ~ i n v e r s e l y r e l a t e d to ~ the initial l e v e l of A C h output. The s t i m u l a t e d (5 Hz) o u t f l o w of N A w a s i n c r e a s e d by i n d o m e t h a c i n (50 /uM) a n d d e c r e a s e d b y P G E 2 (30 nM). T h e s e r e § u l t s s u g g e s t e d that PGEo might p h y s i o l o g i c a l l y m o d u l a t e c h o l i n e r g i ~ transmission whereas adrenergic transmission could be a f f e c t e d only p h a r m a c o l o g i c a l l y .
~
RADIOIMMUNOASSAY OF 13, 14-DIHYDRO-15-KETOPROSTAGLANOIN Fo=. E Youssefnsjadian, H Brodovcky, M Jo~Mson and I Craft.
STIMULATION OF PROBTAGLANDIN SYNTHESIS BY TUMOR-PROMOTING PHORBOL-12,13-DIESTERS IN CANINE KIDNEY (MDCK) CELLS. K. 0huchi, L Levine. J. Biol. Chem. 253: 47834790, 1978.
Department of Biochemical Endocrinology and Institute of Obstetrics and Gynaseology, Chelsea Hospital for Women, London SW3
Tumor-promoting 12-O-tetradecanoyl-phorbol-13-aeetate and phsrbol-12,13-di-decanoate, but not the non-tumor promoting 4~-phorbol-12,13-di-decanoate, stimulated deacylation of cellular llpids, prostaglandin hiosynthesis, and morphological changes in cultured MDCK cells. The increased prostaglandin biosynthesis and morphological changes required at least 24 hrs for expression. Cycloheximide inhibited the stimulated prostaglandin biosynthesis, the changes in morphology and the increased lipid deacylation. Indomsthacin (0.5 pg/ml) completely inhibited the stimulated prostaglandin biosynthesis and also inhibited some deaeylation of cellular lipids. Indomethacin, however, did not affect the 12-0-tetradeeanoyl-phorbol-13-acetatestimulated changes in morphology.
A simple method is descrlbed for the dsterminatlon of 13, 14-dihydro-15-keto-prostaglandin F2a(PGFM), using a highly specific antiserum ralssd in New Zealand rabbits. It involves extraction of human peripheral venous plasma with diethyl ether after addition of tritiated PGFM and HC1. Radioimmunoassay is performed on appropriate aliquots; aftsr 2 hours or overnight equilibration the bound and free metabol i t t e r s separated using dextran-coated charcoal. The mean values + S.D. obtained ars as follows: hsalthy males 32 ± 16 pg/ml, fsmalss during follicular phass 48 + 18 pg/ml, luteal phase 37 + 8 pg/ml, first t~imestsr of pregnancy 66 ~ 33 pg/ml, second trimester 67 ± 42 pg/ml and third trimester 72 ± 26 pg/ml. 81