Adenylyl cyclase in the heart: An enzymocytochemical and immunocytochemical approach

Schulze, Wolfgang; Buchwalow, Igor

doi:10.1002/(sici)1097-0029(19980301)40:6<473::aid-jemt7>3.0.co;2-q

Cited by 12 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As demonstrated previously in guinea‐pig neurones, treating membrane preparations to remove N‐linked glycosylation and prevent G protein association causes a shift of labelled protein to the expected molecular mass (Liu et al 1999). The idea that guinea‐pig cardiac myocytes express significant levels of AC4 protein is consistent with the previous immunohistochemical evidence that the AC4 antibody specifically labels cardiac tissue (Schulze & Buchwalow, 1998).…”

Section: Discussionsupporting

confidence: 88%

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

Belevych

Sims

Harvey

2001

The Journal of Physiology

View full text Add to dashboard Cite

The effects that muscarinic receptor stimulation have on the cAMP‐dependent regulation of L‐type Ca2+ currents were studied in isolated guinea‐pig ventricular myocytes using the whole‐cell configuration of the patch‐clamp technique. The muscarinic agonist ACh inhibited the Ca2+ current stimulated by the β‐adrenergic agonist isoprenaline (Iso), and washout of ACh revealed a stimulatory response that appeared as a transient rebound increase in the amplitude of the Ca2+ current. The ACh‐induced stimulatory effect was not observed in the absence of Iso. ACh‐induced rebound stimulation was also observed in the presence of H2 histamine receptor activation and cholera toxin treatment, which like β‐adrenergic receptor activation enhance adenylyl cyclase (AC) activity in a stimulatory G protein (Gs)‐dependent manner. ACh‐induced rebound stimulation was not observed in the presence of forskolin, which enhances AC activity in a Gs‐independent manner. Pertussis toxin (PTX) treatment blocked both the stimulatory and inhibitory effects of ACh. Intracellular dialysis with QEHA, a peptide that binds free G protein βγ subunits, selectively antagonized the stimulatory effect, leaving an enhanced inhibitory effect. Evidence for the expression of AC4, an isoform of AC that can be stimulated by Gβγ but only in the presence of Gαs, was obtained by Western blot analysis of guinea‐pig ventricular myocyte membrane preparations. These results suggest that muscarinic receptor stimulation facilitates as well as inhibits cAMP‐dependent regulation of the Ca2+ current and that the net response is a balance between these two actions. We suggest that the stimulatory effect is due to a direct activation of AC4 by the βγ subunits of a PTX‐sensitive G protein.

show abstract

Section: Discussionsupporting

confidence: 88%

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

Belevych

Sims

Harvey

2001

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…In addition, a large number of signaling proteins, classically associated with receptor-mediated events at the cell surface including heterotrimeric G proteins [(8, 40, 151), reviewed in (26,28,141)], AC isoforms (118,147), phospholipase A 2 (117), phospholipase C␤ (59) and phospholipase D (35), regulator of G protein signaling (RGS) proteins [reviewed in (11)], ␤-arrestin-1 (120,135), GPCR kinases (52,148,149), A kinase anchoring proteins, and PKA (113), among others, have been demonstrated to be trafficked to the nucleus and/or nuclear membrane. Interestingly, enzymes involved in the generation and metabolism of phosphoinositides (4) or the processing of peptide ligands such as angiotensin-converting enzyme (81) and endothelin-converting enzyme-1 (51) have also been localized to the nuclei of different cell types.…”

Section: Nuclear Gpcr-mediated Signalingmentioning

confidence: 99%

Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling

Vaniotis

Allen

Hébert

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

In recent years, we have come to appreciate the complexity of G protein-coupled receptor signaling in general and β-adrenergic receptor (β-AR) signaling in particular. Starting originally from three β-AR subtypes expressed in cardiomyocytes with relatively simple, linear signaling cascades, it is now clear that there are large receptor-based networks which provide a rich and diverse set of responses depending on their complement of signaling partners and the physiological state. More recently, it has become clear that subcellular localization of these signaling complexes also enriches the diversity of phenotypic outcomes. Here, we review our understanding of the signaling repertoire controlled by nuclear β-AR subtypes as well our understanding of the novel roles for G proteins themselves in the nucleus, with a special focus, where possible, on their effects in cardiomyocytes. Finally, we discuss the potential pathological implications of alterations in nuclear β-AR signaling.

show abstract

“…14,15 In heart, AC5 and AC6 represent the dominant isoforms, 14 although AC7 and AC9 may be present at the mRNA level, 16,17 and AC4 both at the mRNA and protein level. 18,19 AC5 and AC6 share strong similarities, both in sequence and functional characteristics: both are activated by G␣ s subunits and forskolin and inhibited by G␣ i and G␤␥ subunits, 20,21 Ca 2ϩ ions, 22,23 and PKA phosphorylation. 14,15,20,24,25 However, AC5 and AC6 differ in their regulation by PKC: AC5 is activated, 26 whereas AC6 is inhibited, 27 by PKC phosphorylation.…”

Section: Cyclic Amp Synthesismentioning

confidence: 99%

Compartmentation of Cyclic Nucleotide Signaling in the Heart

Fischmeister

Castro

Abi-Gerges

et al. 2006

Circulation Research

327

251

View full text Add to dashboard Cite

Abstract-A current challenge in cellular signaling is to decipher the complex intracellular spatiotemporal organization that any given cell type has developed to discriminate among different external stimuli acting via a common signaling pathway. This obviously applies to cAMP and cGMP signaling in the heart, where these cyclic nucleotides determine the regulation of cardiac function by many hormones and neuromediators. Key Words: cAMP Ⅲ cGMP Ⅲ heart Ⅲ G protein-coupled receptor Ⅲ phosphodiesterase T he cyclic nucleotides cyclic adenosine 3Ј,5Ј-monophosphate (cAMP) and cyclic guanosine 3Ј,5Ј-monophosphate (cGMP) were identified more than 4 decades ago. 1,2 Since then, many studies have appeared on how these 2 second messengers are synthesized or degraded, what makes their level go up or down, what they do to target effectors by either covalent (phosphorylation) or noncovalent (direct binding to proteins, such as ion channels or guanine-nucleotide-exchange factors) mechanisms, and how they affect a countless number of cellular functions. [3][4][5][6] In certain tissues and organs, the cyclic nucleotide pathways have been so fully explored over the years that one can wonder what else is there to be found. This is the case for cAMP in the heart, where it plays a key role in the sympathetic nerve/␤-adrenergic receptor (␤-AR)/adenylyl cyclase (AC)/protein kinase A (PKA) axis that serves to stimulate cardiac rhythm (chronotropy) as well as contractile force (inotropy) and relaxation (lusitropy). 7 Yet, there are a number of questions that have always made us wonder but have only lately begun to receive the attention they deserve: how so many different receptors coupled to cAMP or cGMP signaling pathway manage to achieve specific cellular responses? What is the purpose of the different adenylyl and guanylyl cyclases present in the same cell? Why do Original

show abstract

Adenylyl cyclase in the heart: An enzymocytochemical and immunocytochemical approach

Cited by 12 publications

References 33 publications

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling

Compartmentation of Cyclic Nucleotide Signaling in the Heart

Contact Info

Product

Resources

About

Adenylyl cyclase in the heart: An enzymocytochemical and immunocytochemical approach

Cited by 12 publications

References 33 publications

ACh‐induced rebound stimulation of L‐type Ca2+ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

ACh‐induced rebound stimulation of L‐type Ca2+ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

Nuclear GPCRs in cardiomyocytes: an insider's view of β-adrenergic receptor signaling

Compartmentation of Cyclic Nucleotide Signaling in the Heart

Contact Info

Product

Resources

About

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase

ACh‐induced rebound stimulation of L‐type Ca²⁺ current in guinea‐pig ventricular myocytes, mediated by Gβγ‐dependent activation of adenylyl cyclase