Subclasses of cyclic AMP phosphodiesterase in cardiac muscle

Weishaar, Ronald E.; Kobylarz-Singer, Dianne C.; Kaplan, Harvey

doi:10.1016/s0022-2828(87)80574-6

Cited by 61 publications

(31 citation statements)

References 14 publications

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“…Therefore, selective inhibition of the low Km cyclic AMP PDE in cerebral cortex is sufficient to elevate cellular cyclic AMP concentration. Ro 20 1724 which selectively inhibits the same isoenzyme as rolipram (Davis, 1984;Weishaar et al, 1987), although somewhat less potently, showed similar activity, but diminished potency, in comparison to rolipram, in the assay used in the present study.…”

Section: Discussionmentioning

confidence: 54%

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Challiss

Nicholson²

1990

British J Pharmacology

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1 The effects of selective inhibition of phosphodiesterase activities on the concentration and rate of hydrolysis of adenosine 3': 5' cyclic-monophosphate (cyclic AMP) in rat cerebral cortical slices has been studied. 2 Isoprenaline caused a rapid, concentration-dependent increase in cyclic AMP concentration to new steady-state levels (basal: 7.1 + 0.7; 10M isoprenaline: 14.3 + 1.4 pmolmg'1 protein). Addition of a 13-adrenoceptor antagonist to isoprenaline-stimulated cerebral cortical slices caused a rapid decrease in cyclic AMP concentration to basal levels (t 12: 58 + 18 s). 3 Preincubation of slices for 30min with the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine, denbufylline, rolipram or Ro2O 1724 caused concentration-dependent increases in basal and isoprenalinestimulated cyclic AMP concentrations and decreased the rate of cyclic AMP hydrolysis measured after .addition of a P-adrenoceptor antagonist. However, SKF 94120 and zaprinast had none of these effects.4 The results are discussed with respect to previous studies of phosphodiesterase isozymic activities isolated from cerebrum and it is suggested that the Ca2+/calmodulin-independent, low Km cyclic AMP phosphodiesterase isozyme, which is selectively inhibited by denbufylline, rolipram and Ro2O 1724, and is present in cerebrum is of critical importance to the regulation of cyclic AMP concentration in this tissue.

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Section: Discussionmentioning

confidence: 54%

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Challiss

Nicholson²

1990

British J Pharmacology

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“…It is also supported by a large body of evidence for distinct intracellular localization of the di erent PDE subtypes. For instance, a substantial amount of PDE3 and PDE4 activity was found in a membrane-bound fraction of rat cardiomyocytes (Weishaar et al, 1987;Kaasic & Ohisalo, 1996;Okruhlicova et al, 1996) which may accentuate the role of these PDE subtypes in the control of sarcolemmal processes, such as cyclic AMP-dependent phosphorylation of L-type Ca 2+ channels. PDE3 and PDE4 have also a 5 ± 30 fold lower K m for cyclic AMP than PDE2 (Bode et al, 1991;Beavo, 1995), which should attenuate the role of PDE2 in I Ca regulation when [cAMP] i near the membrane is low.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L‐type Ca²⁺ current in rat ventricular myocytes

Verde

Vandecasteele

Lezoualc’h

et al. 1999

British J Pharmacology

167

146

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1 The e ects of several phosphodiesterase (PDE) inhibitors on the L-type Ca current (I Ca ) and intracellular cyclic AMP concentration ([cAMP] i ) were examined in isolated rat ventricular myocytes. The presence of mRNA transcripts encoding for the di erent cardiac PDE subtypes was con®rmed by RT ± PCR. 2 IBMX (100 mM), a broad-spectrum PDE inhibitor, increased basal I Ca by 120% and [cAMP] i by 70%, similarly to a saturating concentration of the b-adrenoceptor agonist isoprenaline (1 mM). However, MIMX (1 mM), a PDE1 inhibitor, EHNA (10 mM), a PDE2 inhibitor, cilostamide (0.1 mM), a PDE3 inhibitor, or Ro 20-1724 (0.1 mM), a PDE4 inhibitor, had no e ect on basal I Ca and little stimulatory e ects on [cAMP] i (20 ± 30%). 3 Each selective PDE inhibitor was then tested in the presence of another inhibitor to examine whether a concomitant inhibition of two PDE subtypes had any e ect on I Ca or [cAMP] i . While all combinations tested signi®cantly increased [cAMP] i (40 ± 50%), only cilostamide (0.1 mM)+Ro20-1724 (0.1 mM) produced a signi®cant stimulation of I Ca (50%). Addition of EHNA (10 mM) to this mix increased I Ca to 110% and [cAMP] i to 70% above basal, i.e. to similar levels as obtained with IBMX (100 mM) or isoprenaline (1 mM). 4 When tested on top of a sub-maximal concentration of isoprenaline (1 nM), which increased I Ca by (&40% and had negligible e ect on [cAMP] i , each selective PDE inhibitor induced a clear stimulation of [cAMP] i and an additional increase in I Ca . Maximal e ects on I Ca were &8% for MIMX (3 mM), &20% for EHNA (1 ± 3 mM), &30% for cilostamide (0.3 ± 1 mM) and &50% for Ro20-1724 (0.1 mM). 5 Our results demonstrate that PDE1-4 subtypes regulate I Ca in rat ventricular myocytes. While PDE3 and PDE4 are the dominant PDE subtypes involved in the regulation of basal I Ca , all four PDE subtypes determine the response of I Ca to a stimulus activating cyclic AMP production, with the rank order of potency PDE44PDE34PDE24PDE1.

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“…PDEs were isolated from several vascular beds (rabbit aorta and pulmonary artery, bovine aorta) using the method previously described by Weishaar and coworkers, 17 or using a modification of the procedure described by Lugnier et al 18 This latter method differed from previous isolation procedures in that the adsorption column contained diethylaminoethyl (DEAE)-Trisacryl M instead of DEAEcellulose, and the proteins were eluted using different salt gradients to increase resolution. After connective tissue and adventia were removed, 2-4 g vascular muscle from each bed was minced into 0.5 mm squares with a Mcllwayne tissue chopper (Brinkman Instrs., Westbury, New York), and suspended in 10 volumes (wt/vol) of buffer A (20 mM Tris-HCl, pH 7.5, containing 2 mM magnesium acetate, 1 mM dithiothreitol, and 5 mM Na 2 EDTA).…”

Section: Procedures For Isolating Phosphodiesterasesmentioning

confidence: 99%

“…In preliminary experiments, the supernatant was applied to DEAEcellulose and eluted with sodium acetate as described previously. 17 In subsequent experiments, the supernatant was applied to a DEAE-Trisacryl M column. The column was washed with several bed volumes of buffer B (20 mM Tris-HCl, pH 7.5, containing 2 mM magnesium acetate, 1 mM dithiothreitol, and proteinase inhibitors) and eluted by two successive linear NaCl gradients (0.05-0.15 M, 300 ml total; 0.15-0.40 M, 200 ml total).…”

Section: Procedures For Isolating Phosphodiesterasesmentioning

confidence: 99%

Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor.

Weishaar¹,

Kobylarz-Singer²,

Keiser³

et al. 1990

Hypertension

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Two subclasses of cyclic guanosine monophosphate (GMP) -specific phosphodiesterases were identified in vascular tissue from several beds. The activity of one subclass (phosphodiesterase IB) was stimulated severalfold by calmodulin and selectively inhibited by the phosphodiesterase inhibitor TCV-3B. The activity of the other subclass (phosphodiesterase IC) was not stimulated by calmodulin and was selectively inhibited by the phosphodiesterase inhibitor M&B 22,948. To assess the involvement of both subclasses in regulating cyclic GMP-dependent responses, the ability of TCV-3B and M&B 22,948 to potentiate the in vitro and in vivo responses to the endogenous guanylate cyclase stimulator atrial natriuretic factor (ANF) was evaluated. Both TCV-3B and M&B 22,948 relaxed isolated rabbit aortic and pulmonary artery rings and also potentiated the relaxant effect of ANF. In addition, both inhibitors produced small increases in urine flow and sodium excretion in anesthetized rats and potentiated the diuretic and natriuretic responses to exogenous ANF. M&B 22,948 (30 /tg/kg/min) produced a threefold increase in the natriuretic response to simultaneously administered ANF, and TCV-3B (10 /tg/kg/min) produced a twofold increase in the response to ANF. The results of the present experiments suggest that both the calmodulin-sensitive and calmodulin-insensitive subclasses of cyclic GMP-specific phosphodiesterase play a role in regulating the in vitro and in vivo response to ANF. {Hypertension 1990;15:528-540) T he role of atrial natriuretic factor (ANF) in regulating vascular muscle contractile function, diuresis and natriuresis, and secretion of renin and aldosterone is well known (for reviews see References 1 and 2). Murad and others have suggested that many of these actions are because of stimulation by ANF of a membrane-bound form of guanylate cyclase, leading to an increase in intracellular levels of the second messenger cyclic guanosine monophosphate (GMP). 34 The link between cyclic GMP and ANF is supported by the observation that inhibitors of guanylate cyclase such as methylene blue block the vascular relaxant response to ANF 5 and by the observation that changes in circulating

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Subclasses of cyclic AMP phosphodiesterase in cardiac muscle

Cited by 61 publications

References 14 publications

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L‐type Ca²⁺ current in rat ventricular myocytes

Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor.

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Subclasses of cyclic AMP phosphodiesterase in cardiac muscle

Cited by 61 publications

References 14 publications

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Effects of selective phosphodiesterase inhibition on cyclic AMP hydrolysis in rat cerebral cortical slices

Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L‐type Ca2+ current in rat ventricular myocytes

Subclasses of cyclic GMP-specific phosphodiesterase and their role in regulating the effects of atrial natriuretic factor.

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Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L‐type Ca²⁺ current in rat ventricular myocytes