Adenylyl cyclase signaling inhibition

Cell signaling. Environmental tobacco smoke, administered to rats during gestation, the early neonatal period, or both, elicited induction of total adenylyl cyclase. In the brain, the specific coupling of p-adren-ergic receptors to adenylyl cyclase was inhibited in the smoke-treated groups, despite... 

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

Opioid receptors generally mediate neuronal inhibition. They couple to G or G0> and produce inhibition of Ca2+ channels and opening of K+ channels. They also inhibit adenylyl cyclase. Through this and other downstream signaling pathways, opioid receptors modulate... 

Fig. 3. Signal transduction of the tt2A-D79N adrenergic receptor. Mutation of the aspartic acid residue 79 in the second transmembrane domain of the mouse a2A adrenergic receptor to asparagine (D79N) selectively uncoupled this receptor mutant from activation of currents in vitro without interfering with Ca channel or adenylyl cyclase inhibition (Surprenant et al. 1992). In vivo, the a2A D79N receptor was expressed at 20% of the level of the wild-type a2A-receptor (MacMillan et d. 1996), and Ca channel inhibition was also blunted (a) (Lakhlani et al. 1997)...

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

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