The role of cyclic nucleotides and calcium in the relaxation produced by amrinone in rat aorta

Zypp, Andrea van der; Rechtman, M. P.; Majewski, H.

doi:10.1016/s0306-3623(00)00071-9

Cited by 14 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, Liu et al (18) recently reported that in portal vein myocytes, ␤-adrenoceptor stimulation profoundly inhibits SOCC-induced Ca 2ϩ currents. In agreement with results in vascular smooth muscle (18,34), the present study found that cAMP (either by ␤-adrenoceptor activation or by direct elevation) inhibits SOCC in porcine ASM. Furthermore, the present study demonstrates that cAMP effects on SOCC in ASM are largely mediated via protein kinase A.…”

Section: Effect Of Cyclic Nucleotides On [Ca 2ϩ ] I In Asmsupporting

confidence: 92%

“…However, data on cyclic nucleotide modulation of SOCC in smooth muscle are relatively novel and limited. For example, in rat aorta, cAMP has been found to inhibit SOCC (34), whereas in astrocytes there appears to be enhancement of SOCC-mediated Ca 2ϩ influx by cAMP (37). However, Liu et al (18) recently reported that in portal vein myocytes, ␤-adrenoceptor stimulation profoundly inhibits SOCC-induced Ca 2ϩ currents.…”

Section: Effect Of Cyclic Nucleotides On [Ca 2ϩ ] I In Asmmentioning

confidence: 99%

See 1 more Smart Citation

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle

Iyanoye

Sieck³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

([Ca 2ϩ ]o), nifedipine, and KCl (preventing Ca 2ϩ influx through L-type and SOCC channels). SOCC was then activated by reintroduction of [Ca 2ϩ ]o and characterized by several techniques. We examined cAMP effects on SOCC by activating SOCC in the presence of 1 M isoproterenol or 100 M dibutryl cAMP (cell-permeant cAMP analog), whereas we examined cGMP effects using 1,2-diolate (DETA-NO nitric oxide donor) or 100 M 8-bromoguanosine 3',5'-cyclic monophosphate (cell-permeant cGMP analog). The role of protein kinases A and G was examined by preexposure to 100 nM KT-5720 and 500 nM KT-5823, respectively. SOCC-mediated Ca 2ϩ influx was dependent on the extent of SR Ca 2ϩ depletion, sensitive to Ni 2ϩ and La 3ϩ , but not inhibitors of voltage-gated influx channels. cAMP as well as cGMP potently inhibited Ca 2ϩ influx, predominantly via their respective protein kinases. Additionally, cAMP cross-activation of protein kinase G contributed to SOCC inhibition. These data demonstrate that a Ni 2ϩ /La 3ϩ -sensitive Ca 2ϩ influx in ASM triggered by SR Ca 2ϩ depletion is inhibited by cAMP and cGMP via a protein kinase mechanism. Such inhibition may play a role in the bronchodilatory response of ASM to clinically relevant drugs (e.g., ␤-agonists vs. nitric oxide).capacitative calcium entry; trachea; adenosine 3Ј,5Ј-cyclic monophosphate; guanosine 3Ј,5Ј-cyclic monophosphate; nitric oxide; isoproterenol AIRWAY SMOOTH MUSCLE (ASM) tone represents a balance between bronchoconstriction and bronchodilation. The goal of clinical therapy for pathophysiological states such as asthma, allergy, and inflammation is to prevent excessive bronchoconstriction, both in the acute and chronic setting, and to restore a balance by producing bronchodilation. Cytosolic (intracellular) Ca 2ϩ concentration ([Ca 2ϩ ] i ) is a key determinant of ASM tone (12,23,33 The cyclic nucleotides cyclic adenosine 3Ј,5Ј-cyclic monophosphate (cAMP) and cyclic guanosine 3Ј,5Ј-cyclic monophosphate (cGMP) mediate the effects of a variety of endogenous substances as well as clinically relevant drugs, e.g., ␤ 2 -agonists and nitric oxide (NO), used to produce relaxation of ASM (13,25,28). Cyclic nucleotide effects are mediated in part by downregulation of mechanisms that would normally elevate [Ca 2ϩ ] i in ASM. Previously, we demonstrated that salbutamol, a ␤ 2 -agonist (28), as well as NO donors (26) inhibit ACh-induced [Ca 2ϩ ] i oscillations in ASM that occur via repetitive SR Ca 2ϩ release and reuptake. Both cAMP and cGMP also influence the plasma membrane via membrane hyperpolarization (9, 15) and inhibition of Ca 2ϩ influx via L-type Ca 2ϩ channels (16,17). Given the relative novelty but somewhat ubiquitous expression of SOCC, there is currently limited and sometimes inconsistent data on cyclic nucleotide modulation of Ca 2ϩ influx via this mechanism in tissues other than ASM. In rat aorta, cAMP inhibits SOCC (34) but enhances it in astrocytes (37). We hypothesize that cyclic nucleotides inhibit SOCC, preventing [Ca 2ϩ ] i elevation as well as S...

show abstract

Section: Effect Of Cyclic Nucleotides On [Ca 2ϩ ] I In Asmsupporting

confidence: 92%

Section: Effect Of Cyclic Nucleotides On [Ca 2ϩ ] I In Asmmentioning

confidence: 99%

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle

Iyanoye

Sieck³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Therefore, it is thought that the relaxation induced by MBCQ, zaprinast or dipyridamole is not due to an increase of cAMP content in rat ileal smooth muscle. Recently, it was reported that the vasorelaxant action of amrinone, a PDE III inhibitor, did not involve cyclic nucleotides in the rat aorta (van der Zypp et al, 2000). Moreover, we reported that papaverine, a nonselective PDE inhibitor, inhibits muscle contraction mainly by increasing cAMP and/or cGMP levels due to inhibition of PDE in vascular smooth muscle, but mainly by inhibiting mitochondrial respiration in ileal smooth muscle (Kaneda et al, 1998).…”

Section: Discussionmentioning

confidence: 90%

“…However, it has been reported that the vasorelaxant action of amrinone, a PDE III inhibitor, dose not involve cyclic nucleotides (van der Zypp et al, 2000). Moreover, we reported that papaverine, a nonselective PDE inhibitor, inhibits vascular smooth muscle contraction mainly by increasing cAMP and/or cGMP levels as a result of its inhibition of PDE, but that it acts mainly by inhibiting mitochondrial respiration in ileal smooth muscle (Kaneda et al, 1998).…”

Section: Introductionmentioning

confidence: 76%

Lack of Cyclic Nucleotide Regulation of MBCQ-induced Relaxation of Rat Ileal Smooth Muscle.

Kaneda

Yamamoto

Azegami

et al. 2003

J. Smooth Muscle Res.

View full text Add to dashboard Cite

The effects of the type V phosphodiesterase (PDE V) inhibitors, MBCQ, zaprinast and dipyridamole, on the relationship between relaxation and cyclic nucleotide content were investigated in rat ileal smooth muscle. Each of MBCQ (0.01-10 µM), zaprinast (0.1-100 µM) and dipyridamole (0.1-100 µM) inhibited carbachol (CCh; 10 µM)-induced contractions in a concentration-dependent manner. When compared with the concentrations of these agents producing 50% relaxation (IC50) of CCh-induced contraction, MBCQ was 14-20 fold more potent than the other agents. The inhibitory potency of these agents against high K + (65 mM KCl)-induced contractions were similar to that for CCh. MBCQ (1, 10 µM) did not significantly increase the cGMP content above control levels in the presence of CCh (10 µM). Both Zaprinast (1-100 µM) and dipyridamole (1-100 µM) increased the cGMP content of smooth muscle preparations in a concentration-dependent manner. There was a positive correlation between the inhibition of the CCh-induced contraction and the increase in cGMP content elicited by zaprinast and dipyridamole (zaprinast; r=0.72, P<0.05, dipyridamole; r=0.92, P<0.05). However, MBCQ at a concentration which induced a medium-sized relaxation did not significantly increase the cGMP content. Neither MBCQ, zaprinast nor dipyridamole significantly increased the cAMP content of the preparations above control. In summary, it is suggested that the inhibition of CCh-induced contractions by zaprinast and dipyridamole involves increases in cGMP content via inhibition of PDE V. However the inhibition of CCh-induced contraction by MBCQ may not involve cyclic nucleotides in rat ileal smooth muscle.

show abstract

“…6,7) Some PDEs, including PDE-3, are responsible for inducing vascular relaxation in different vascular beds when they are inhibited, including in aortas of rats. [8][9][10] Inhibitors of PDEs increase cytosolic levels of cAMP and cGMP and cause vasodilation by activating protein kinases A (PKA) and G (PKG). This activation induces many cellular effects, such as the uptake of intracellular Ca 2+ by the sarcoplasmic reticulum, dephosphorylation of the myosin light chain, inhibition of Ca 2+ influx, activation of K + channels and hyperpolarization of the plasma membrane.…”

mentioning

confidence: 99%

Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase

Martins

Pazini

Alves

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

This study describes the synthetic route and molecular computational docking of LQFM 021, as well as examines its biological effects and toxicity. The docking studies revealed strong interaction of LQFM 021 to phosphodiesterase-3 (PDE-3). In isolated arteries, the presence of endothelium potentiates the relaxation for LQFM 021 and the inhibition cyclic nucleotides reduced the relaxation. Pre-contraction with KCl (45 mM), the treatment with tetraethylammonium (TEA) (5 mM) and inhibition of reticular Ca(2+)-ATPase showed an inhibitory effect on relaxation. Moreover, the compound reduced the contraction evoked by the Ca(2+) influx. Acute toxicity tests revealed that the compound was practically nontoxic. In conclusion, this study showed that a new synthetic derivative of pyrazole is a possible PDE-3 inhibitor and has vasorelaxant activity and low toxicity.

show abstract

The role of cyclic nucleotides and calcium in the relaxation produced by amrinone in rat aorta

Cited by 14 publications

References 39 publications

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle

Lack of Cyclic Nucleotide Regulation of MBCQ-induced Relaxation of Rat Ileal Smooth Muscle.

Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase

Contact Info

Product

Resources

About

The role of cyclic nucleotides and calcium in the relaxation produced by amrinone in rat aorta

Cited by 14 publications

References 39 publications

Cyclic nucleotide regulation of store-operated Ca2+influx in airway smooth muscle

Cyclic nucleotide regulation of store-operated Ca2+influx in airway smooth muscle

Lack of Cyclic Nucleotide Regulation of MBCQ-induced Relaxation of Rat Ileal Smooth Muscle.

Synthesis, Docking Studies, Pharmacological Activity and Toxicity of a Novel Pyrazole Derivative (LQFM 021)—Possible Effects on Phosphodiesterase

Contact Info

Product

Resources

About

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle

Cyclic nucleotide regulation of store-operated Ca²⁺influx in airway smooth muscle