Second-messenger roles

Immune system cells called T cells can pump in a wave of magnesium to send a signal. F. Y. Li et al. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. 2011. Nature 475(7357), p. 471. DOI 10.1038/naturel0246. 

McPhail LC, Clayton CC, Snyderman R. A potential second messenger role for unsaturated fatty acids activation of Ca -depen-dent protein kinase. Science 1984 224 622-625. 

Arachidonate is mobilized in the cell s interior, and all eicosanoid-synthesizing enzymes are intracellular. Yet, aside from second messenger roles, such as those illustrated in the previous sections, all other actions of the eicosanoids take place in the extracellular milieu, where these molecules can interact with transmembrane receptors. How do the eicosanoids exit the cells in which they are produced ... 

Earl Sutherland of Vanderbilt University won the 1971 Nobel Prize in physiology or medicine for uncovering the role of cAMP as a second messenger in connection with his studies of the fight or flight hormone epineph rine (Section 27 6)... 

Another type of NR crosstalk, which has only recently been recognized, is the so-called nongenomic actions of several receptors that induce very rapid cellular effects. Effectively, evidence has accumulated over several decades that steroid receptors may have a role that does not require their transcriptional activation, such as modifying the activity of enzymes and ion channels. While the effects of steroids that are mediated by the modulation of gene expression do occur with a time lag of hours, steroids can induce an increase in several second messengers such as inositol triphosphate, cAMP, Ca2+, and the activation of MARK and PI3 kinase within seconds or minutes. Many mechanistic details of these nongenomic phenomena remain poorly understood. Notably, controversy still exists as to the identity of the receptors that initiate the non-genomic steroid actions. However, it now appears that at least some of the reported effects can be attributed to the same steroid receptors that are known as NRs. 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Bonisch, H, Hammermann, R and Bruss, M (1998) Role of protein kinase C and second messengers in regulation of the norepinephrine transporter. Adv. Pharmacol. 42 183-186. 

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