Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro.
Alprostadil
/ pharmacology
Animals
Cyclic GMP
/ metabolism
Dose-Response Relationship, Drug
Electric Stimulation
In Vitro Techniques
Male
Muscle Contraction
/ drug effects
Muscle, Smooth
/ drug effects
Nitric Oxide
/ metabolism
Rats, Wistar
Receptor Cross-Talk
Signal Transduction
Sildenafil Citrate
/ pharmacology
Urinary Bladder
/ drug effects
Alprostadil
Detrusor muscle
NO/cGMP pathway
PGE
Sildenafil
Urinary bladder
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
15
10
2018
revised:
09
02
2019
accepted:
11
03
2019
pubmed:
14
6
2019
medline:
17
1
2020
entrez:
14
6
2019
Statut:
ppublish
Résumé
Sildenafil (PDE5-inhibitor) and alprostadil (PGE Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS, 4Hz, 80V, 1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean ± SEM (n = 5-7). Alprostadil (0.01-10 μM) concentration-dependently potentiated ACh (100μM)- and EFS (4 Hz)- induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40 ± 5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1 μM), but inhibited it at higher ones (10-100 μM). IBMX (non-selective PDE-inhibitor, 0.01-100μM) and SNP (NO-donor, 1nM-1 mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1μM), L-NAME (non-selective NOS-inhibitor, 100μM), N-PLA (nNOS-inhibitor, 30μM) or MB (nonselective GC-inhibitor, 10μM). In presence of sildenafil (0.1μM), the concentration-response curve of alprostadil (0.01-10μM) on both ACh and EFS-induced contraction was clearly shifted downward. A crosstalk between PGE
Sections du résumé
BACKGROUND
BACKGROUND
Sildenafil (PDE5-inhibitor) and alprostadil (PGE
METHODS
METHODS
Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS, 4Hz, 80V, 1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean ± SEM (n = 5-7).
RESULTS
RESULTS
Alprostadil (0.01-10 μM) concentration-dependently potentiated ACh (100μM)- and EFS (4 Hz)- induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40 ± 5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1 μM), but inhibited it at higher ones (10-100 μM). IBMX (non-selective PDE-inhibitor, 0.01-100μM) and SNP (NO-donor, 1nM-1 mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1μM), L-NAME (non-selective NOS-inhibitor, 100μM), N-PLA (nNOS-inhibitor, 30μM) or MB (nonselective GC-inhibitor, 10μM). In presence of sildenafil (0.1μM), the concentration-response curve of alprostadil (0.01-10μM) on both ACh and EFS-induced contraction was clearly shifted downward.
CONCLUSIONS
CONCLUSIONS
A crosstalk between PGE
Identifiants
pubmed: 31195343
pii: S1734-1140(18)30616-9
doi: 10.1016/j.pharep.2019.03.004
pii:
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Sildenafil Citrate
BW9B0ZE037
Alprostadil
F5TD010360
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
659-668Informations de copyright
Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.