Adenylyl cyclase signaling, disruption

Adenylyl cyclase in learning and memory. The cAMP-signal transduction cascade has been demonstrated to play a role critical to the formation of long-term memory in both cellular models and in animals. The specific adenylyl cyclases involved are being identified by current research. In AC1 mutant mice there is a partial disruption of long-term potentiation (LTP), a cellular model of... 

Isolated right ventricular tissues were used to measure the contribution of P-AR signaling to contractility. Cardiac inotropy was monitored in isolated, paced right ventricular muscle strips. Preparations from pr AR-KO mice failed to show any responsiveness to isoproterenol administration, while wild-type preparations showed robust inotropic responses (28). This lack of contractile response is not caused by generalized hyporesponsiveness of the contractile apparatus because prAR-KO ventricles responded normally to activators of adenylyl cyclase such as forskolin. Surprisingly, disruption of both pr and P2-ARs has only modest effects on resting left ventricular contractility in vivo. When contractility was assessed with a micromanometer-tipped catheter, -i-dP/dt was reduced by 20% and -dP/dt was reduced by 12% in p /prAR-KO mice compared to wild-type mice (30). 

Thompson MD, Cole DE, Jose P (2008) The pharmacogenomics of G protein-coupled receptor signaling insight from health and disease. Methods Mol Biol 448 77-108 Thompson MD, Percy ME, Burnham WM et al (2008) G Protein-coupled receptors disrupted in human genetic disease. Methods Mol Biol 448 109-138 Monsma FJ Jr, Mahan LC, McVittie LD et al (1990) Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc Natl Acad Sci USA 87 6723-6727... 

Inhibitory neurons of the ENS release a variety of transmitters and cotransmitters, including nitric oxide (NO), ATP (acting on P2Y receptors), VIP, and pituitary adenylyl cyclase-activating peptide (PACAP) NO is a primary inhibitory transmitter. Interstitial cells of Cajal (ICC) relay signals from the nerves to the smooth muscle cells to which they are electrically coupled. The ICC have receptors for both the inhibitory transmitter NO and the excitatory tachykinins. Disruption of the ICC impairs excitatory and inhibitory neurotransmission. 

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