Linked Life Data

8834493

Source:http://linkedlifedata.com/resource/pubmed/id/8834493

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1996-12-10
pubmed:abstractText
The involvement of various phosphodiesterases (PDEs) in controlling the time-dependent mechanical properties of guinea pig trachealis smooth muscles was determined by using different classes of PDE inhibitors as pharmacological tools. These drugs produced low amplitude and long-lasting dose-dependent relaxations on the resting tone with the following EC50 values: rolipram, 3 nM; indolidan, 0.11 microM; and zaprinast, 0.5 nM and 1 microM. These PDE inhibitors were 50% less active than 1 microM norepinephrine. The effects of the drugs were also tested on carbachol-induced contractions and norepinephrine-evoked relaxations. Zaprinast, but not rolipram nor indolidan, decreased the rate of rise of contraction, thus prolonging the time to reach the plateau by 75% without modifying the magnitude of the responses. Zaprinast and rolipram significantly increased the total length of the norepinephrine effect by 25 and 35%, respectively. Similar results were obtained in a dose-dependent manner on isoproterenol-induced relaxations. In contrast, a higher concentration of indolidan was required to affect the amplitude, duration, and time to peak of isoproterenol- or norepinephrine-induced relaxations. These results indicate that PDE IV (rolipram sensitive) and PDE I, and less likely PDE V (both zaprinast sensitive), are involved in the control of guinea pig airway contractile kinetics, whereas PDE III (indolidan sensitive) is essentially involved in the modulation of the resting tone. Four cytosolic isozymes were identified in bovine airway smooth muscles (ASMs); PDE I (calmodulin-dependent PDE), PDE II (cGMP-stimulated PDE), PDE IV (cAMP-specific and rolipram-sensitive PDE), and PDE V (cGMP-specific and zaprinast-sensitive PDE). Characterization of PDE isoforms present in the microsomal fraction by HPLC showed the presence of PDE IV, PDE V, and to a lesser extent PDE III. However, PDE III was not detected in ASM cytosol. Using newly synthesized radioligands, binding studies confirmed the low level of expression of PDE III and the presence of PDE IV. We conclude that PDE I controls the rate of contraction, whereas PDE V and PDE IV prolong the time of relaxation induced by NE. PDE V would control the ASM responsiveness by regulating the intracellular cGMP concentration, which in turn would both activate PKG and stimulate PDE II (cGS-PDE). Since the various isozymes of PDE are differently involved in the kinetic control of the mechanical events in ASM, they represent physiologically relevant and important pharmacological targets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-4212
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1784-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Specific cyclic nucleotide phosphodiesterase inhibitors differently modulate contractile kinetics in airway smooth muscle.
pubmed:affiliation
Département de physiologie et biophysique, Université de Sherbrooke, QC, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't