Receptors second-messenger pathways

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Gopalakrishnan, M., Molinari, E., Sullivan, J. Regulation of human 0 ,P2 neuronal nicotinic acetylcholine receptors by cholinergic channel ligands and second messenger pathways. Mol. Pharmacol. 52 524, 1997. 

Currently, three subtypes of histamine receptors are proposed and H2 receptors are found in peripheral tissues and the central nervous system (CNS), and receptors are found in the CNS. The second messenger pathway that mediates Hrreceptor stimulation is... 

Multiple interactions are also being demonstrated between the traditional second-messenger pathways and the MAPK cascades. Free (3y G protein subunits, generated upon activation of receptors coupled to the G family, lead to activation of the ERK pathway. The mechanism by which this occurs, which may involve an interaction between the subunits and Ras or Raf, is a subject of intensive research (see Ch. 19). In addition, increases in cellular Ca2+ concentrations lead to stimulation of the ERK pathway, apparently via phosphorylation by CaMKs of proteins, for example She and Grb, that link growth factor receptor tyrosine kinases to Ras. Activation of the... 

Sweet, bitter and umami taste involve receptor-coupled second-messenger pathways that are differentially expressed across the gustatory epithelium 827... 

Mouradian, R.D., Seller, F.M., and Waterhouse, B.D. (1991) Noradrenergic potentiation of excitatory transmitter action in cerebro-cortical slices evidence of mediation by an alphaj-receptor-linked second messenger pathway. Brain Res 546 83-95. 

The cAMP second messenger pathway. Key proteins include hormone receptors (Rec), a stimulatory G protein (Gs), catalytic adenylyl cyclase (AC), phosphodiesterases (PDE) that hydrolyze cAMP, cAMP-dependent kinases, with regulatory (R) and catalytic (C) subunits,... 

Figure 2 Known second-messenger pathways that modulate capsaicin or VRs. GPCR, G protein-coupled receptors PLA2, phospholipase A2 AC, adenylate cyclase IP3, inositoltriphosphate DAC diacylglycerol LM, lipoxygenase metabolites AA, arachidonic acid ANA, anandamide PG, prostaglandins Gq/11, Gq/j, Gs, trimeric G-proteins (adapted from Premkumar, 2001)...

Adenosine A3 receptors have been shown to couple to classical or G protein-dependent second-messenger pathways through activation of both Gi family and Gq family G proteins (Palmer et al. 1995 Merighi et al. 2003 Hasko and Cronstein 2004). 

The entry of calcium into neurons via presynaptic calcium channels is a key step in evoked neurotransmitter release. Compromised calcium channel function can lead to severe neurological consequences, and yet the pharmacological inhibition of specific calcium channel subtypes can be beneficial in the treatment of conditions such as neuropathic pain. Because of the importance of these channels, neurons have evolved complex means for regulating calcium channel activity, including activation of second messenger pathways by G protein coupled receptors and feedback inhibition by calcium binding proteins. By these means, neurons are able to maintain the fine balance of cytoplasmic calcium levels that is required for optimal neurotransmitter release. 

Boekhoff I., Michel W. C., Breer H. and Ache B. W. (1994). Single odors differentially stimulate dual second messenger pathways in lobster olfactory receptor cells. J. Neurosci. 14, 3304-3309. 

The endogenous purine mediator adenosine, originating from adenosine 5-triphosphate (ATP), is a widely distributed neuromodulator with complex effects (Sawynok, 1998 Sawynok and Liu, 2003). Four adenosine receptors have been identified and are termed Al, A2A, A2B, and A3 (Fredholm et al., 2001). They are all GPCRs and couple to classical second messenger pathways Al and A3 receptor activation decreases the level of cAMP, A2 increases it, whereas A2B receptor stimulates PLC (Sawynok, 1998 Sawynok and Liu, 2003). 

Oocytes contain many, but not all, of the activities required for the coupling of receptors to their second messenger pathways. However, as with any expression system, there are several important caveats in using oocytes in gene isolation and protein characterization (Snutch, 1988). 

Go G-protein involved in coupling receptors to the cAMP second messenger pathway, inhibiting adenylyl cyclase. Overlaps with G class. 

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