EP receptor-mediated inhibition by prostaglandin E<sub>1</sub>of cardiac L-type Ca<sup>2+</sup>current of rabbits

Yamamoto, Taku; Habuchi, Yoshizumi; Tanaka, Hideo; Suto, Fumiaki; Morikawa, Junichiro; Kashima, Kei; Yoshimura, Manabu

doi:10.1152/ajpheart.1999.277.4.h1369

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…If this is occurring, exposure to PGE1 should antagonize or inhibit the stimulatory response to βAR activation. Consistent with this possibility, PGE1 has been reported to inhibit cAMP‐dependent regulation of Ca 2+ channel function in rabbit atrial myocytes (Yamamoto et al 1999). However, we found that exposure to 10 μ m PGE1 did not inhibit the stimulatory response to a submaximal concentration of Iso (Fig.…”

Section: Resultsmentioning

confidence: 70%

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

Warrier

Gopalakrishnan

Eckert

et al. 2007

The Journal of Physiology

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Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by β-adrenergic receptor (βAR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca 2+ current in guinea pig ventricular myocytes. This is despite finding evidence that these cells express EP 4 prostaglandin receptors, which are known to activate G s -dependent signalling pathways. Using fluorescence resonance energy transfer-based biosensors that are either freely diffusible or bound to A kinase anchoring proteins, we demonstrate that the difference is due to the ability of isoproterenol to stimulate cAMP production in cytosolic and caveolar compartments of intact cardiac myocytes, while PGE1 only stimulates cAMP production in the cytosolic compartment. Unlike other receptor-mediated responses, compartmentation of PGE1 responses was not due to concurrent activation of a G i -dependent signalling pathway or phosphodiesterase activity. Instead, compartmentation of the PGE1 response in cardiac myocytes appears to be due to transient stimulation of cAMP in a microdomain that can communicate directly with the bulk cytosolic compartment but not the caveolar compartment associated with βAR regulation of L-type Ca 2+ channel function.

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Section: Resultsmentioning

confidence: 70%

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

Warrier

Gopalakrishnan

Eckert

et al. 2007

The Journal of Physiology

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“…Although less common than upregulation, G-protein-dependent inhibition of L-type Ca 2ϩ channels is not totally unprecedented. A similar mechanism of L-type Ca 2ϩ channel inhibition has been demonstrated for the action of neuropeptide Y, somatostatin, galanin (Degtiar et al, 1997;Zeng et al, 1999), prostaglandins (Yamamoto et al, 1999), opioids, and catecholamines (Hernandez-Guijo et al, 1999). The long-lasting nature of the CART action may be surprising, considering the putative G-protein-dependent mechanism.…”

Section: Discussionmentioning

confidence: 69%

Cocaine- and Amphetamine-Regulated Transcript Peptide Modulation of Voltage-Gated Ca²⁺Signaling in Hippocampal Neurons

et al. 2001

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Administration of cocaine and amphetamine increases cocaine- and amphetamine-regulated transcript (CART) expression in the rat striatum (Douglass et al., 1995). CART mRNA is highly expressed in different parts of the human and rat brain, including hippocampus (Douglass et al., 1995; Couceyro et al., 1997; Kuhar and Yoho, 1999; Hurd and Fagergren, 2000). The presence of CART peptide 55-102 immunoreactivity in dense core vesicles of axon terminals suggests that the peptide may be released and may act as a neuromodulator (Smith et al., 1997) to induce neurophysiological and behavioral effects. Little is known, however, about CART peptide-responsive cells, receptor(s), or intracellular signaling mechanisms that mediate CART peptide action. Here we show that CART peptide 55-102 inhibits voltage-dependent intracellular Ca(2+) signaling and attenuates cocaine enhancement of depolarization-induced Ca(2+) influx in rat hippocampal neurons. The inhibitory effect of CART peptide 55-102 on Ca(2+) signaling is likely mediated by an inhibition of L-type voltage-gated Ca(2+) channel activity via a G-protein-dependent pathway. These results indicate that voltage-gated Ca(2+) channels in hippocampal neurons are targets for CART peptide 55-102 and suggest that CART peptides may be important in physiology and behavior mediated by the hippocampus, such as certain forms of learning and memory.

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“…Interestingly, PGE 1 stimulation is known to protect myocardial tissue from injury following ischemia and reperfusion, 35 an effect that has been suggested to depend on PGE-mediated stimulation of EP 3 receptors in cardiac myocytes 36 and the consequent G i -mediated inhibition of cAMP synthesis. 37 In summary, the present work provides original insight into the mechanisms that underpin cAMP/PKA specificity of response by demonstrating that, in cardiac myocytes, both PKA-RI and PKA-RII isoforms subsets anchor to subcellular Figure 8. Model of PKA isoforms compartmentalization.…”

Section: Discussionmentioning

confidence: 78%

Protein Kinase A Type I and Type II Define Distinct Intracellular Signaling Compartments

Benedetto

Zoccarato

Lissandron

et al. 2008

Circulation Research

185

206

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Abstract-Protein kinase A (PKA) is a key regulatory enzyme that, on activation by cAMP, modulates a wide variety of cellular functions. PKA isoforms type I and type II possess different structural features and biochemical characteristics, resulting in nonredundant function. However, how different PKA isoforms expressed in the same cell manage to perform distinct functions on activation by the same soluble intracellular messenger, cAMP, remains to be established. Here, we provide a mechanism for the different function of PKA isoforms subsets in cardiac myocytes and demonstrate that PKA-RI and PKA-RII, by binding to AKAPs (A kinase anchoring proteins), are tethered to different subcellular locales, thus defining distinct intracellular signaling compartments. Within such compartments, PKA-RI and PKA-RII respond to distinct, spatially restricted cAMP signals generated in response to specific G protein-coupled receptor agonists and regulated by unique subsets of the cAMP degrading phosphodiesterases. Key Words: cAMP Ⅲ compartmentalization Ⅲ compartmentation Ⅲ adrenergic stimulation Ⅲ prostaglandin Ⅲ protein kinase A P rotein kinase A (PKA) is a key regulatory enzyme in the heart that is involved in the catecholamine-mediated control of excitation-contraction coupling, as well as in a myriad of other functions including activation of transcription factors and control of metabolic enzymes. The second messenger cAMP activates PKA by binding to the regulatory (R) subunits, causing release of the activated catalytic (C) subunits.The fact that, following cAMP-engagement, PKA mediates a plethora of cellular responses has raised the question of how specificity is maintained. In recent years, features of this pathway that contribute to specificity have been uncovered. 1 A key role is played by AKAPs (A kinase anchoring proteins), a family of proteins that act as molecular scaffolds to anchor PKA in the vicinity of specific substrate molecules, 2 thus focusing PKA activity toward relevant substrates.A second mechanism contributing to specificity revolves around the spatial control of the cAMP signal itself. Restriction of intracellular diffusion of cAMP has been shown by using a variety of approaches, [3][4][5] including direct imaging of gradients of cAMP in response to activation of various G protein-coupled receptors (GPCRs). 6 A key role in shaping cAMP intracellular pools is played by phosphodiesterases (PDEs), the enzymes that hydrolyze cAMP. 7 Indeed, individual PDE isoforms have been shown to be functionally coupled to specific GPCRs to degrade cAMP selectively in response to a given stimulus. 8 Cardiac myocytes express all four types of PKA isozymes, PKA-RI␣, PKA-RII␣, PKA-RI␤, and PKA-RII␤. 9 PKA isoforms show different subcellular localization, with PKA-RII being mainly associated with the particulate fraction of cell lysates whereas PKA-RI has been found preferentially in the cytosol. 10,11 PKA isoforms also show different biochemical properties. PKA-RI is more readily dissociated by cAMP than PKA-RII, 12,13 an...

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EP receptor-mediated inhibition by prostaglandin E₁of cardiac L-type Ca²⁺current of rabbits

Cited by 7 publications

References 26 publications

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

Cocaine- and Amphetamine-Regulated Transcript Peptide Modulation of Voltage-Gated Ca²⁺Signaling in Hippocampal Neurons

Protein Kinase A Type I and Type II Define Distinct Intracellular Signaling Compartments

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EP receptor-mediated inhibition by prostaglandin E1of cardiac L-type Ca2+current of rabbits

Cited by 7 publications

References 26 publications

cAMP microdomains and L‐type Ca2+ channel regulation in guinea‐pig ventricular myocytes

cAMP microdomains and L‐type Ca2+ channel regulation in guinea‐pig ventricular myocytes

Cocaine- and Amphetamine-Regulated Transcript Peptide Modulation of Voltage-Gated Ca2+Signaling in Hippocampal Neurons

Protein Kinase A Type I and Type II Define Distinct Intracellular Signaling Compartments

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EP receptor-mediated inhibition by prostaglandin E₁of cardiac L-type Ca²⁺current of rabbits

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

cAMP microdomains and L‐type Ca²⁺ channel regulation in guinea‐pig ventricular myocytes

Cocaine- and Amphetamine-Regulated Transcript Peptide Modulation of Voltage-Gated Ca²⁺Signaling in Hippocampal Neurons