Hypersensitivity of Gi protein mediated muscarinic receptor adenylyl cyclase in chronic ischaemic heart failure in the rat

1993 ◽  
Vol 27 (11) ◽  
pp. 2065-2070 ◽  
Author(s):  
L.-X. Fu ◽  
Q.-P. Feng ◽  
Q.-M. Liang ◽  
X.-Y. Sun ◽  
T. Hedner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Gi Protein

Immunocytochemical studies of the Gi Protein mediated muscarinic receptor-adenylyl cyclase system

1995 ◽  
pp. 161-168
Author(s):  
Wolfgang Schulze ◽  
Wolf-Peter Wolf ◽  
Michael L. X. Fu ◽  
Rosemarie Morwinski ◽  
Igor B. Buchwalow ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Adenylyl Cyclase System ◽  
Gi Protein ◽  
Immunocytochemical Studies

Immunocytochemical studies of the Gi Protein mediated muscarinic receptor-adenylyl cyclase system

1995 ◽  
Vol 147 (1-2) ◽  
pp. 161-168 ◽  
Author(s):  
Wolfgang Schulze ◽  
Wolf-Peter Wolf ◽  
Michael L. X. Fu ◽  
Rosemarie Morwinski ◽  
Igor B. Buchwalow ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Adenylyl Cyclase System ◽  
Gi Protein ◽  
Immunocytochemical Studies

Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes

Nature ◽  
1988 ◽  
Vol 334 (6181) ◽  
pp. 434-437 ◽  
Author(s):  
Ernest G. Peralta ◽  
Avi Ashkenazi ◽  
John W. Winslow ◽  
J. Ramachandran ◽  
Daniel J. Capon
Keyword(s):  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Differential Regulation ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Pi Hydrolysis

Adrenergic and muscarinic receptor regulation and therapeutic implications in heart failure

1996 ◽  
Vol 157 (1-2) ◽  
Author(s):  
Wilhelm Schmitz ◽  
Peter Boknik ◽  
Bettina Linck ◽  
FrankU. M�ller
Keyword(s):  
Heart Failure ◽  
Muscarinic Receptor ◽  
Receptor Regulation ◽  
Therapeutic Implications

scholarly journals Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Gαq protein-induced cardiomyopathy

2010 ◽  
Vol 299 (5) ◽  
pp. H1459-H1467 ◽  
Author(s):  
Valeriy Timofeyev ◽  
Cliff A. Porter ◽  
Dipika Tuteja ◽  
Hong Qiu ◽  
Ning Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mouse Model ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Adenylyl Cyclase ◽  
Electrical Remodeling ◽  
Kinase C ◽  
Progressive Heart Failure

Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. ACV and ACVI are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation. Specifically, the salutary effects resulting from the disruption of ACV have been established in multiple models of cardiomyopathy. It has been proposed that a continual activation of ACV through elevated levels of protein kinase C could play an integral role in mediating a hypertrophic response leading to progressive heart failure. Elevated protein kinase C is a common finding in heart failure and was demonstrated in murine cardiomyopathy from cardiac-specific overexpression of Gαq protein. Here we assessed whether the disruption of ACV expression can improve cardiac function, limit electrophysiological remodeling, or improve survival in the Gαq mouse model of heart failure. We directly tested the effects of gene-targeted disruption of ACV in transgenic mice with cardiac-specific overexpression of Gαq protein using multiple techniques to assess the survival, cardiac function, as well as structural and electrical remodeling. Surprisingly, in contrast to other models of cardiomyopathy, ACV disruption did not improve survival or cardiac function, limit cardiac chamber dilation, halt hypertrophy, or prevent electrical remodeling in Gαq transgenic mice. In conclusion, unlike other established models of cardiomyopathy, disrupting ACV expression in the Gαq mouse model is insufficient to overcome several parallel pathophysiological processes leading to progressive heart failure.

An M2 muscarinic receptor subtype coupled to both adenylyl cyclase and phosphoinositide turnover

Science ◽  
1987 ◽  
Vol 238 (4827) ◽  
pp. 672-675 ◽  
Author(s):  
A Ashkenazi ◽  
J. Winslow ◽  
E. Peralta ◽  
G. Peterson ◽  
M. Schimerlik ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Receptor Subtype ◽  
Muscarinic Receptor Subtype ◽  
Phosphoinositide Turnover ◽  
M2 Muscarinic Receptor

Lidocaine attenuates muscarinic receptor-mediated inhibition of adenylyl cyclase in airway smooth muscle

2003 ◽  
Vol 470 (1-2) ◽  
pp. 65-71 ◽  
Author(s):  
Motonari Yunoki ◽  
Tsutomu Nakahara ◽  
Akiko Mitani ◽  
Takeshi Maruko ◽  
Yuko Kubota ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle

Basenji-greyhound dog: increased m2 muscarinic receptor expression in trachealis muscle

1995 ◽  
Vol 268 (6) ◽  
pp. L935-L940 ◽  
Author(s):  
C. W. Emala ◽  
A. Aryana ◽  
M. A. Levine ◽  
R. P. Yasuda ◽  
S. A. Satkus ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adenylyl Cyclase ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Receptor Expression ◽  
Smooth Muscle Relaxation ◽  
Muscarinic Agonists ◽  
M2 Muscarinic Receptor ◽  
Muscarinic M2 Receptors

Airway smooth muscle from asthmatic humans and from the Basenji-greyhound dog (BG) dog is hyporesponsive to beta-adrenergic agonist stimulation. Because adenylyl cyclase is under dual regulation in airway smooth muscle, we compared muscarinic receptor-coupled inhibition of adenylyl cyclase in airway smooth muscle from BG and mongrel dogs. Inhibition of forskolin-stimulated adenylyl cyclase activity by the muscarinic M2 agonist oxotremorine was greater in airway smooth muscle membranes from BG compared with mongrel controls. Quantitative immunoprecipitation studies showed increased numbers of m2 but not m3 muscarinic receptors in the BG airway smooth muscle. The enhanced ability of muscarinic agonists to inhibit adenylyl cyclase in BG airway smooth muscle may be due to the greater numbers of muscarinic m2 receptors, which may account in part for impaired airway smooth muscle relaxation in the BG model of airway hyperresponsiveness.

Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L221-L229 ◽  
Author(s):  
H. Kume ◽  
K. Mikawa ◽  
K. Takagi ◽  
M. I. Kotlikoff
Keyword(s):  
Smooth Muscle ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Muscarinic Receptor ◽  
G Proteins ◽  
Isometric Tension ◽  
Guanine Nucleotide Binding Protein ◽  
Kca Channels ◽  
Stimulatory G Protein ◽  
Guanine Nucleotide Binding

We have examined the functional consequences of G protein coupling to calcium-activated potassium (KCa) channels using isometric tension records from guinea pig tracheal smooth muscle. After incubation with 1 microgram/ml pertussis toxin (PTX) for 6 h, the contraction response to 1 microM methacholine (MCh) was suppressed by 31.7 +/- 5.0% (n = 10). Similarly, the contraction was inhibited by 29.1 +/- 5.0% (n = 6) after application of 0.1 microM AF-DX 116, an M2-selective muscarinic receptor antagonist. Cholera toxin (CTX, 2.0 micrograms/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), also suppressed contraction by 43.9 +/- 3.3% (n = 11). The inhibitory effects of PTX, AF-DX 116, or CTX were reversed in the presence of 100 nM charybdotoxin (ChTX), a selective KCa channel inhibitor. These findings suggest that disruption of inhibitory coupling between muscarinic receptor and KCa channels mediated by PTX-sensitive G proteins, or KCa channel activation induced by Gs/adenylyl cyclase-linked processes, antagonizes muscarinic contraction. The isoproterenol concentration-inhibition curves for precontracted trachea (1 microM MCh) were shifted to the left after perfusion with PTX or AF-DX 116, and the leftward shift of the curve was blocked by ChTX. Thus direct or indirect regulation of KCa channels mediated by the inhibitory guanine nucleotide binding protein (Gi) and Gs may play a functionally important role in the mechanical antagonism by the two receptor agonists.

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