Inotropic responses change during postnatal maturation in rabbit

1988 ◽  
Vol 255 (2) ◽  
pp. H335-H342 ◽  
Author(s):  
M. Artman ◽  
P. A. Kithas ◽  
J. S. Wike ◽  
S. J. Strada
Keyword(s):  
Adenylate Cyclase ◽  
Calcium Sensitivity ◽  
Inotropic Response ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase ◽  
Tension Development ◽  
Postnatal Maturation ◽  
High Affinity ◽  
Age Related ◽  
Camp Hydrolysis

Inotropic response to four different types of pharmacological stimuli were compared in isolated right ventricular papillary muscles from newborn (24–48 h of age), immature (14–16 days), and adult (6–7 mo) rabbits. Forskolin, a direct activator of adenylate cyclase, produced a 12.5-fold increase in the maximal rate of tension development in the newborn group. The maximum response to isoproterenol was only 45% of the maximum forskolin response, suggesting incomplete physiological coupling of myocardial beta-adrenergic receptors to adenylate cyclase at birth. In contrast to the substantial inotropic response to agents that stimulate adenosine 3',5'-cyclic monophosphate (cAMP) generation (forskolin and isoproterenol), a selective inhibitor of cAMP hydrolysis (milrinone) was relatively ineffective in the newborn group. Sulmazole, a drug that enhances calcium sensitivity of the contractile proteins, produced its greatest inotropic effect in immature myocardium. Cytosolic high-affinity cAMP phosphodiesterase activity was partially purified from ventricular homogenates by anion-exchange chromatography. The kinetics of cAMP hydrolysis (Km and Vmax) and inhibitory potency of milrinone were comparable in each age group. Thus the age-related differences in inotropic responsiveness may not be attributable to postnatal changes in myocardial cytosolic high-affinity cAMP phosphodiesterase activity.

Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae

1987 ◽  
Vol 7 (10) ◽  
pp. 3629-3636
Author(s):  
J Nikawa ◽  
P Sass ◽  
M Wigler
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cyclic Amp ◽  
Copy Number ◽  
Growth Arrest ◽  
Yeast Cells ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase ◽  
High Affinity ◽  
Cyclic Amp Phosphodiesterase

Saccharomyces cerevisiae contains two genes which encode cyclic AMP (cAMP) phosphodiesterase. We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S. cerevisiae, which encodes a low-affinity cAMP phosphodiesterase. These two genes represent highly divergent branches in the evolution of phosphodiesterases. High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation. PDE1 and PDE2 appear to account for the aggregate cAMP phosphodiesterase activity of S. cerevisiae. Disruption of both PDE genes results in a phenotype which resembles that induced by the RAS2(Val-19) mutation. pde1- pde2- ras1- ras2- cells are viable.

Thyrotrophin and prostaglandin E2 increase calmodulin levels and cyclic AMP phosphodiesterase activity in cultured porcine thyroid cells

1988 ◽  
Vol 117 (1) ◽  
pp. 109-114 ◽  
Author(s):  
N. Takasu ◽  
T. Yamada ◽  
Y. Shimizu
Keyword(s):  
Cyclic Amp ◽  
Prostaglandin E2 ◽  
Prostaglandin E ◽  
Maximal Velocity ◽  
Phosphodiesterase Activity ◽  
Dibutyryl Camp ◽  
Camp Phosphodiesterase ◽  
Thyroid Cells ◽  
Michaelis Constants ◽  
Camp Hydrolysis

ABSTRACT Thyrotrophin (TSH) and prostaglandin E2 (PGE2) increased cellular cyclic AMP (cAMP), calmodulin levels and cAMP phosphodiesterase activity in cultured porcine thyroid cells. Dibutyryl cAMP (dbcAMP), a stable analogue of cAMP, increased calmodulin levels and cAMP phosphodiesterase activity. These results indicate that TSH- and PGE2-stimulated increases in calmodulin are mediated by cAMP. This increased concentration of calmodulin in turn stimulates cAMP phosphodiesterase. Double reciprocal plots of cAMP hydrolysis yielded two apparent Michaelis constants (Km); the lower in the 1 μmol/l and the higher in the 10 μmol/l range. Thyrotrophin, PGE2 and dbcAMP increased the values of maximal velocity without changing the Km values. J. Endocr. (1988) 117, 109–114

scholarly journals Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae.

1987 ◽  
Vol 7 (10) ◽  
pp. 3629-3636 ◽  
Author(s):  
J Nikawa ◽  
P Sass ◽  
M Wigler
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cyclic Amp ◽  
Copy Number ◽  
Growth Arrest ◽  
Yeast Cells ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase ◽  
High Affinity ◽  
Cyclic Amp Phosphodiesterase

Saccharomyces cerevisiae contains two genes which encode cyclic AMP (cAMP) phosphodiesterase. We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S. cerevisiae, which encodes a low-affinity cAMP phosphodiesterase. These two genes represent highly divergent branches in the evolution of phosphodiesterases. High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation. PDE1 and PDE2 appear to account for the aggregate cAMP phosphodiesterase activity of S. cerevisiae. Disruption of both PDE genes results in a phenotype which resembles that induced by the RAS2(Val-19) mutation. pde1- pde2- ras1- ras2- cells are viable.

scholarly journals IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1686
Author(s):  
Adelaida M. Celaya ◽  
Lourdes Rodríguez-de la Rosa ◽  
Jose M. Bermúdez-Muñoz ◽  
José M. Zubeldia ◽  
Carlos Romá-Mateo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inflammatory Cytokines ◽  
Noise Exposure ◽  
Sensorineural Deafness ◽  
Serum Levels ◽  
Genetic Syndromes ◽  
Expression Ratio ◽  
Postnatal Maturation ◽  
Age Related ◽  
Underlying Mechanisms

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

Control of cAMP in lung endothelial cell phenotypes. Implications for control of barrier function

1999 ◽  
Vol 277 (1) ◽  
pp. L119-L126 ◽  
Author(s):  
Troy Stevens ◽  
Judy Creighton ◽  
W. Joseph Thompson
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Barrier Function ◽  
Enzyme Regulation ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Calcium Entry ◽  
Camp Accumulation ◽  
Camp Phosphodiesterase ◽  
Conversion Rates

Pulmonary microvascular endothelial cells (PMVECs) form a more restrictive barrier to macromolecular flux than pulmonary arterial endothelial cells (PAECs); however, the mechanisms responsible for this intrinsic feature of PMVECs are unknown. Because cAMP improves endothelial barrier function, we hypothesized that differences in enzyme regulation of cAMP synthesis and/or degradation uniquely establish an elevated content in PMVECs. PMVECs possessed 20% higher basal cAMP concentrations than did PAECs; however, increased content was accompanied by 93% lower ATP-to-cAMP conversion rates. In PMVECs, responsiveness to β-adrenergic agonist (isoproterenol) or direct adenylyl cyclase (forskolin) activation was attenuated and responsiveness to phosphodiesterase inhibition (rolipram) was increased compared with those in PAECs. Although both types of endothelial cells express calcium-inhibited adenylyl cyclase, constitutive PMVEC cAMP accumulation was not inhibited by physiological rises in cytosolic calcium, whereas PAEC cAMP accumulation was inhibited 30% by calcium. Increasing either PMVEC calcium entry by maximal activation of store-operated calcium entry or ATP-to-cAMP conversion with rolipram unmasked calcium inhibition of adenylyl cyclase. These data indicate that suppressed calcium entry and low ATP-to-cAMP conversion intrinsically influence calcium sensitivity. Adenylyl cyclase-to-cAMP phosphodiesterase ratios regulate cAMP at elevated levels compared with PAECs, which likely contribute to enhanced microvascular barrier function.

scholarly journals Cyclic AMP compartmentation due to increased cAMP‐phosphodiesterase activity in transgenic mice with a cardiac‐directed expression of the human adenylyl cyclase type 8 (AC8)

2003 ◽  
Vol 17 (11) ◽  
pp. 1380-1391 ◽  
Author(s):  
Marie Georget ◽  
Philippe Mateo ◽  
Grégoire Vandecasteele ◽  
Larissa Lipskaia ◽  
Nicole Defer ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Transgenic Mice ◽  
Adenylyl Cyclase ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase
Sign in / Sign up

Export Citation Format

Share Document