Ca2+ channel inhibition

Gai3 41,000 Ca2+ channel (inhibition) PI-Phospholipase C (activation) Phospholipase A2... 

Cabrera-Vera TM, Hernandez S, Earls LR et al (2004) RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic intemeurons. Proc Natl Acad Sci USA 101 16339 14... 

Causes reversible, voltage-independent Ca2+ channel inhibition [93]... 

Multiple actions including block of T-type Ca2+ channels, inhibition of GABA transaminase, and block of axonal Na channels. In addition to seizure states, it is a backup in bipolar disorders and used in migraine treatment. 

Stimulates adenylyl cyclase activity and Ca2+ channels Inhibits adenylyl cyclase activity and activates K+channels Stimulate phospholipase C activity Modulate sodium/hydrogen ion exchanger... 

Quinidine, the classical class IA drug, binds to the open state oftheNa+ channel, and prolongs the action potential by block of the delayed rectifier-. In higher concentrations, L-type Ca2+ channels are inhibited. Quinidine exerts antimuscarinic effects, thereby accelerating AV-nodal... 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

All three classes also inhibit depolarization-induced contraction of venous smooth muscle in vitro. However, venous relaxation does not substantially contribute to the hemodynamic actions of Ca2+ channel blockers. 

The OP group of receptois share common effector mechanisms. All receptois couple via pertussis toxin-sensitive Go and Gi proteins leading to (i) inhibition of adenylate cyclase (ii) reduction of Ca2+ currents via diverse Ca2+ channels (hi) activation of inward rectifying K+ channels. In addition, the majority of these receptors cause the activation of phospholipase A2 (PLA2), phospholipase C 3 (PLC 3), phospholipase D2 and of MAP (mitogen-activated protein) kinase (Table 3). 

Pertussis toxin is produced by the bacterium Bordetella pertussis. It covalently modifies G-proteins of the G/Go family (transfer of a ADP-ribose moiety of NAD onto G-protein a-subunits). ADP-ribosylated G-proteins are arrested in their inactive state and, as a consequence, functionally uncoupled from their respective effectors. Examples for pertussis toxin-sensitive cellular responses include the hormonal inhibition of adenylyl cyclases, stimulation ofK+ channels, inhibition of Ca2+ channels and stimulation ofthe cGMP-phosphodiesterase in retinal rods. 

In CICR, the RyR channel is activated by pM Ca2+ and inhibited by mM Ca2+. This biphasic Ca2+ dependence can be explained by two distinct Ca2+ binding sites high-affinity (XD pM) Ca2+ site for activation (A-site)... 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

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