Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin 3 (ET3) infusion increases the concentration of atrial natriuretic peptide (ANP) in plasma, which in turn raises hematocrit (Hct) through a transcapillary shift of plasma fluid and proteins into the interstitium, thereby reducing plasma volume (PV). The level of ANP bioactivity in peripheral target tissues is a function of ANP secretory rate and the turnover rate of ANP and its intracellular effector mechanisms. Neutral endopeptidase (NEP) is a widely distributed enzyme that participates in ANP catabolism, whereas cGMP-phosphodiesterase (PDE) degrades the intracellular second messenger of ANP. Therefore, we examined the consequences of inhibition of NEP and PDE on the ANP-dependent activity described above using the NEP inhibitor SQ 28,603 and the cGMP-PDE inhibitor zaprinast (M&B 22,948). In anesthetized, bilaterally nephrectomized rats, infusion of SQ 28,603 alone reduced mean arterial pressure (MAP) by 2.5 +/- 0.5% and increased Hct by 4.6 +/- 0.3% (P < .01 for both), leading to a calculated decrease in PV of 7.5 +/- 0.6%. These changes were prevented by pretreatment with rabbit anti-rat ANP antiserum. Simultaneous infusion of ET3 (25 ng/kg/min) and SQ 28,603 caused MAP to increase by 12.8 +/- 2.2%, an effect identical with that observed after ET3 alone (12.7 +/- 2.3%), whereas the increase in Hct of 9.4 +/- 0.4% was greater (P < .05) than the 7.5 +/- 0.4% increase seen with ET3 alone. ET3 increased plasma ANP concentration (599 +/- 135 vs. 108 +/- 13 pg/ml in vehicle-infused rats; P < .0001); ET3 and SQ 28,603 infused simultaneously increased plasma ANP even further (810 +/- 166 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of ANP-dependent effects of endothelin by inhibitors of neutral endopeptidase and cGMP phosphodiesterase. 775 77

Female sexual arousal disorder (FSAD) is the inability to attain or maintain an adequate lubrication-swelling response of sexual excitement. The potentiation of vascular responses leading to increased blood flow in clitoris and vagina has represented the main focus in the pharmacological treatment of FSAD, including the evaluation of the type 5 phosphodiesterase (PDE5) inhibitors. However, due to a lack of clear efficacy, there is no approved pharmacotherapy for FSAD to date. In the present issue of the British Journal of Pharmacology, Wayman et al. show that the administration by intravenous or intravaginal routes of a novel neutral endopeptidase inhibitor, UK-414,445, results in enhanced genital blood flow responses to pelvic nerve stimulation in female rabbits, without significantly affecting blood pressure. Neutral endopeptidase inhibition, by preserving vasoactive peptides such as vasoactive intestinal polypeptide, raises the possibility of a new pharmacological approach to the treatment of FSAD.
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PMID:Neutral endopeptidase inhibition: could it have a role in the treatment of female sexual arousal disorder? 2041 68