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PDE Isoforms (pde + isoform)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Phosphodiesterase Type 4 Inhibition Does Not Restore Ocular Dominance Plasticity in a Ferret Model of Fetal Alcohol Spectrum Disorders

ALCOHOLISM, Issue 3 2010
Thomas E. Krahe
Background:, There is growing evidence that deficits in neuronal plasticity account for some of the neurological problems observed in fetal alcohol spectrum disorders (FASD). Recently, we showed that early alcohol exposure results in a permanent impairment in visual cortex ocular dominance (OD) plasticity in a ferret model of FASD. This disruption can be reversed, however, by treating animals with a Phosphodiesterase (PDE) type 1 inhibitor long after the period of alcohol exposure. Aim:, Because the mammalian brain presents different types of PDE isoforms we tested here whether inhibition of PDE type 4 also ameliorates the effects of alcohol on OD plasticity. Material and Methods:, Ferrets received 3.5 g/Kg alcohol i.p. (25% in saline) or saline as control every other day between postnatal day (P) 10 to P30, which is roughly equivalent to the third trimester equivalent of human gestation. Following a prolonged alcohol-free period (10 to 15 days), ferrets had the lid of the right eye sutured closed for 4 days and were examined for ocular dominance changes at the end of the period of deprivation. Results:, Using in vivo electrophysiology we show that inhibition of PDE4 by rolipram does not restore OD plasticity in alcohol-treated ferrets. Conclusion:, This result suggests that contrary to PDE1, PDE4 inhibition does not play a role in the restoration of OD plasticity in the ferret model of FASD. [source]

Disruption of a Plasmodium falciparum cyclic nucleotide phosphodiesterase gene causes aberrant gametogenesis

MOLECULAR MICROBIOLOGY, Issue 1 2008
Cathy J. Taylor
Summary Phosphodiesterase (PDE) and guanylyl cyclase (GC) enzymes are key components of the cGMP signalling pathway and are encoded in the genome of Plasmodium falciparum. Here we investigate the role of specific GC and PDE isoforms in gamete formation , a process that is essential for malaria transmission and occurs in the Anopheles mosquito midgut following feeding on an infected individual. Details of the intracellular signalling events controlling development of the male and female gametes from their precursors (gametocytes) remain sparse in P. falciparum. Previous work involving the addition of pharmacological agents to gametocytes implicated cGMP in exflagellation , the emergence of highly motile, flagellated male gametes from the host red blood cell. In this study we show that decreased GC activity in parasites having undergone disruption of the PfGC, gene had no significant effect on gametogenesis. By contrast, decreased cGMP-PDE activity during gametocyte development owing to disruption of the PfPDE, gene, led to a severely reduced ability to undergo gametogenesis. This suggests that the concentration of cGMP must be maintained below a threshold in the developing gametocyte to allow subsequent differentiation to proceed normally. The data indicate that PfPDE, plays a crucial role in regulating cGMP levels during sexual development. [source]

Expression and function of phosphodiesterases in nitrofen-induced congenital diaphragmatic hernia in rats

PEDIATRIC PULMONOLOGY, Issue 4 2010
Irene W.J.M. van der Horst MD
Abstract Background Congenital diaphragmatic hernia (CDH) is an anomaly associated with pulmonary hypoplasia and pulmonary hypertension (PH). The limited efficacy of current approaches to treat PH in CDH, including inhaled nitric oxide (NO), drives the search for other therapies. Phosphodiesterases (PDEs) degrade cyclic nucleotide second messenger cAMP and cGMP downstream of NO thereby limiting the vasodilatory response to NO. Objective To identify therapeutic targets by cataloguing the expression and function of PDE isoforms in the pulmonary vasculature in nitrofen-induced CDH in fetal rats. Methods/Results Quantitative RT-PCR revealed PDE1,5 and PDE9 mRNA expression in pulmonary arteries (PAs) of control and nitrofen-induced CDH term fetal rats. In this order of potency, the PDE inhibitors Sildenafil (PDE5),>,EHNA (PDE2),>,Rolipram (PDE4),>,Cilostamide (PDE3) all dilated isolated third generation PA after pre-constriction with the thromboxane analog U46619. Hyperoxic pre-incubation of PAs significantly attenuated vasodilatation induced by the PDE5 inhibitor Sildenafil (65% vs. 33%, P,<,0.004). CDH PAs dilated significantly less to PDE2 inhibitor EHNA compared to control (51% vs. 72%, P,<,0.05). Subsequently PDE2 protein expression was higher in PAs of CDH animals. Conclusion Most PDE isoforms exist in the PAs of fetal rats and their inhibition causes pulmonary vasodilatation. PDE5 inhibition was the most potent vasodilator, however, there were no differences between groups. PDE5-induced vasodilatation was attenuated by hyperoxic pre-incubation. PDE inhibitors might be considered therapeutic targets in combination with iNO in neonates with CDH. Pediatr Pulmonol. 2010; 45:320,325. © 2010 Wiley-Liss, Inc. [source]

Expression of Messenger Ribonucleic Acid Encoding for Phosphodiesterase Isoenzymes in Human Female Genital Tissues

THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007
Stefan Uckert PhD
ABSTRACT Objectives., The use of inhibitors of phosphodiesterase 5 (PDE5) has been suggested to treat symptoms of female sexual dysfunction (FSD). Nonetheless, there has been a relatively low success rate of PDE5 inhibitors in FSD in comparison with male erectile dysfunction. The elevated expression of PDE5 in the human penile erectile tissue is considered the reason for the high clinical efficacy of PDE5 inhibitors in the pharmacotherapy of male erectile dysfunction. Aim., To evaluate by means of molecular biology the expression of messenger ribonucleic acid expression (mRNA) encoding for cyclic AMP and cyclic GMP PDE isoenzymes in female genital tissues. Main Outcome Measures., The amount of mRNA transcripts specifically encoding for cyclic AMP- and/or cyclic GMP-degrading PDE isoenzymes was determined. Methods., Human clitoral, labial, and vaginal tissue was obtained from four female cadavers (age at death: 18,42 years). The expression of mRNA specifically encoding for PDE1A, 1B, 1C, 2A, 4A, 5A, 10A, and 11A was elucidated by means of real-time polymerase chain reaction (PCR) analysis (TaqMan). Human penile erectile tissue (corpus cavernosum [HCC]) was used as a reference tissue. Results., mRNA encoding for all PDE isoforms mentioned above is expressed in the female genital tissues. Different magnitudes of mRNA expression were observed: a predominant expression of mRNA encoding for PDE1A but only insignificant amounts of PDE1B, 1C, 4A, 10, and 11A mRNA were registered. With PDE1A being the only exception, the mRNA expression was always higher in the HCC than in the female genital tissues. Especially, the expression of mRNA encoding for PDE5 was several-fold higher in the HCC. Conclusion., On the mRNA level, various PDE isoforms are expressed in the clitoris, labia, and vagina. It remains to be established as to whether the low expression of PDE5 in female genital tissue might be a negative predictor for the success of PDE5 inhibitors in the treatment of FSD. Uckert S, Ellinghaus P, Albrecht K, Jonas U, and Oelke M. Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues. J Sex Med 2007;4:1604,1609. [source]