ABSTRACT
Abnormal placentation is a potential cause of maternal morbidity and mortality from massive postpartum bleeding. The objective of this study was to investigate the efficacy of occlusive balloons when used as an adjunct to surgery in reducing blood loss and transfusion requirements. A retrospective study of 42 patients was performed involving consecutive cases of abnormal placentation who delivered with either conventional surgery with preoperatively placed occlusive balloons or conventional surgery alone. No differences were noted between the control group and the group of patients who had occlusive balloons with regard to estimated blood loss (P = 0.767), packed red blood cells transfused (P = 0.799), amount of crystalloids infused (P = 0.435), total procedure duration (P = 0.076), and length of ICU stay (P = 0.315) or total hospital stay (P = 0.254). Prophylactic intravascular balloon catheters did not benefit women with abnormal placentation when compared with conventional surgery alone.
Subject(s)
Obstetric Surgical Procedures/instrumentation , Placenta Accreta/surgery , Adult , Female , Humans , Placentation , Pregnancy , Retrospective StudiesSubject(s)
Heart Defects, Congenital/genetics , Limb Deformities, Congenital/genetics , Mutation/genetics , Chromosome Mapping , Chromosomes, Human, Pair 12/genetics , DNA Mutational Analysis , Exons/genetics , Female , Genetic Testing , Genetic Variation/genetics , Genotype , Heart Block/genetics , Heart Septal Defects/genetics , Humans , Introns/genetics , Male , Molecular Sequence Data , Pedigree , Phenotype , Polymorphism, Single-Stranded Conformational , Syndactyly/genetics , SyndromeABSTRACT
Prolonged activation of an A2A adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A2A desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A2A desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724) effectively blocks the increase in PDE activity in desensitized cells. Thus, PDE4 appears to be the PDE specifically activated during A2A desensitization in PC12 cells. Prolonged treatment of PC12 cells with an A2A-selective agonist (CGS21680) leads to increased PDE4 activity in a dose-dependent manner, which can be blocked by an A2A-selective antagonist [8-(3-chlorostyryl)caffeine]. Using two PDE4 antibodies, we were able to demonstrate that the levels of two PDE4-immunoreactive bands (72 and 79 kDa) were increased significantly during A2A desensitization. Prolonged treatment with forskolin to elevate intracellular cyclic AMP contents also resulted in increased PDE4 activity. In addition, activation of PDE4 activity during A2A desensitization could be blocked by a protein kinase A (PKA)-selective inhibitor (H89) and was not observed in a PKA-deficient PC12 cell line (A123). Taken together, activation of PDE4 via a cyclic AMP/PKA-dependent pathway plays a critical role in dampening the signal of the A2A receptor.
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases , 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology , Adenosine/analogs & derivatives , Cyclic AMP/metabolism , Phenethylamines/pharmacology , Phosphoric Diester Hydrolases/biosynthesis , Receptors, Purinergic P1/physiology , Sulfonamides , Adenosine/pharmacology , Adrenal Gland Neoplasms , Animals , Blotting, Western , Caffeine/analogs & derivatives , Caffeine/pharmacology , Colforsin/analogs & derivatives , Colforsin/pharmacology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 4 , Enzyme Activation , Enzyme Inhibitors/pharmacology , Isoquinolines/pharmacology , Kinetics , PC12 Cells , Pheochromocytoma , Phosphodiesterase Inhibitors/pharmacology , Phosphoric Diester Hydrolases/isolation & purification , Polymerase Chain Reaction , Purinergic P1 Receptor Agonists , Rats , Receptor, Adenosine A2A , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purificationABSTRACT
We have previously reported that phosphorylation of adenylyl cyclase type VI (AC6) may result in the suppression of adenylyl cyclase activity during desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC12 cells. In the present study, we demonstrate that protein kinase C (PKC) is responsible for the phosphorylation and inhibition of AC6 during A2a desensitization. Inhibition of PKC by several independent methods markedly blocked the suppression of AC6 during A2a desensitization. Purified PKC from rat brain directly phosphorylated and inhibited recombinant AC6 expressed in Sf21 cells. Substantially lower AC6 activities were also observed in PC12 cells overexpressing PKCdelta or PKCepsilon. Stimulation of A2a-R in PC12 cells under the same conditions as those required for A2a desensitization resulted in an increase in Ca2+-independent PKC activity. Most importantly, exogenous PKC did not further suppress AC6 activity in A2a-desensitized membranes. In vitro PKC phosphorylation of AC6 isolated from A2a-desensitized cells was also profoundly lower than that from control cells, suggesting a specific role for PKC in regulating AC6 during A2a desensitization in PC12 cells. Taken together, our data demonstrate that a calcium-independent, novel PKC inhibits AC6 activity during A2a desensitization in PC12 cells. Independent regulation of AC6 by calcium-independent PKC and by Ca2+ provides an exquisite mechanism for integrating signaling pathways to fine-tune cAMP synthesis.
Subject(s)
Adenylyl Cyclases/metabolism , Cyclic AMP/metabolism , Protein Kinase C/metabolism , Receptors, Purinergic P1/metabolism , Signal Transduction , Animals , PC12 Cells , RatsABSTRACT
In the present study, we demonstrate that the Ca(2+)-inhibitable adenylyl cyclase (AC) activity in the striatum exhibits a daily oscillation with a peak occurring around 10:00 h. A circadian fluctuation of the AC activity evoked by an A2a adenosine-selective agonist was also observed. Intrastriatal injection of an A2a-selective adenosine agonist or antagonist during the interval in which the Ca(2+)-inhibitable AC activity was at its peak resulted in a more significant alteration of locomotor activity than those observed at a later interval. The marked circadian variation in the Ca(2+)-inhibitable AC activity in the striatum appears to cause a circadian fluctuation in the action of at least one neuromodulator.