Second messenger pathways activation

By interfering with any one of the many phases associated with these second messenger pathways, toxins may alter channel gating. For example, the blue green algal toxins, aplysiatoxin, and lyngbyatoxin bind to and activate protein kinase C in a manner similar to phorbol esters (73). They also stimulate arachidonic acid metabolism (74). The coral toxin, palytoxin, also stimulates arachidonic acid breakdown albeit by an unknown mechanism (74) and affects other biochemical activities of the cell (see chapters by Fujiki et al., Wattenberg et al., and Levine et al., this volume). 

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... 

C. Second messengers mediate activation of signaling pathways downstream of the G protein-coupled receptors. 

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. 

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). 

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