Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific binding of 3H-labeled prostaglandin (PG) F2alpha to bovine corpus luteum cell membranes was a rapid (K1=1.1 X 10(4) M(-1)S(-1) and reversible (K(-1)=3.3 X 10(-4) S(-1)) process at 22 degrees C. The specific binding was also a saturable process exhibiting two classes of receptors with apparent dissociation constants (Kds) of 1.6 X 10(-9) M and 2.4 X 10(-8) M. The heterogenous nature of [3H]PGF2alpha binding does not appear to be due to negative cooperatively but merely to represent the existence of two independent groups of receptor sites with discrete affinities. Free energy changes of +11.9 and +10.3 Kcal/mol were calculated from the Kds of high and low affinity receptors, respectively. The binding of [3H]PGF2alpha to the membranes was not accompanied by any detectable changes in receptor-bound or free [3H]PGF2alpha. Addition of increasing amounts of unlabeled PGF2alpha resulted in a dose-dependent inhibition of [3H]PGF2alpha binding to the membranes, with complete inhibition occurring at 10(-6) M. Other unlabeled PGs such as PGF1alpha, PGE2 (5-fold), PGE1 (120-fold), PGA1 and PGB1 (about 10,000-fold) were less effective when compared to unlabeled PGF2alpha in inhibiting [3H] PGF2alpha binding to the membranes. The metabolites of PGF2alpha, 15-keto-PGF2alpha and 13,14-dihydro-15-keto-PGF2alpha had 100-fold less affinity for PGF2alpha receptors. 15(S)15-Methyl-PGF2alpha, an analogue of PGF2alpha, had a fairly high affinity but lower than its parent molecule. Various unsaturated fatty acids, indomethacin and 7-oxa-13-prostynoic acid had 3,000- to 10,000-fold less affinities for PGF2alpha receptors. Incubation of membranes with various enzymes revealed that PGF2alpha receptor molecules are protein in nature which require membrane lipids and specific phospholipids for binding function. Among the various phospholipids used, sphingomyelin was found to be very effective in restoring the loss of [3H]PGF2alpha binding in phospholipase C-treated membranes. N-Ethylmaleimide, but not other SH group alkylating agents inhibited binding. The binding was also inhibited by tetranitromethane, dinitrofluorobenzene and acetic anhydride. This suggested that tyrosyl, histidyl, tryptophan and amino (any one or all of them) but not SH groups were involved in binding interaction.
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PMID:Properties of prostaglandin F2alpha receptors in bovine corpus luteum cell membranes. 1 62

Prostaglandins inhibit the proliferation of the murine P815 mastocytoma. The mechanism of this antitumour activity remains undefined. In several cell systems, the action of PGs is inhibited at the cell surface receptor by pertussis toxin likely through regulatory G proteins involved in the inhibition of adenyl cyclase or activation of phospholipase C. We therefore determined the effect of prostaglandins on the biochemical consequences of activation of these pathways; i.e. concentrations of cyclic AMP (cAMP) and cytosolic free Ca+2 concentrations [( Ca/2]i) respectively. PGD2 (6 ug/mL), PGE1 (10 ug/mL) and PGB1 (50 ug/mL) maximally inhibited (3H)-thymidine incorporation to DNA. PGF2 alpha did not affect DNA synthesis. PGE1 (10 ug/mL) induced a three fold increase in cAMP concentrations. In contrast, the other prostaglandins did not alter cAMP concentrations. Maximal growth inhibitory doses of PGD2, PGE1 and PGB1 decrease [Ca+2]i, as measured by the fluorescence of Indo-1, from 320 +/- 5 nM to 172 +/- 20 nM, 161 +/- 12 nM, and 151 +/- 18 nM respectively. PGF2 alpha did not alter [Ca+2]i. Therefore, in contrast to the effects on cAMP, the decrease in [Ca+2]i was concordant with the inhibition of DNA synthesis. This suggests that PGs may inhibit proliferation through decreasing [Ca+2]i in the P815 mastocytoma.
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PMID:Prostaglandins inhibit proliferation of the murine P815 mastocytoma by decreasing cytoplasmic free calcium levels [( Ca+2]i). 314 77