Cyclic AMP

Abstract

Cyclic adenosine monophosphate (cAMP) was the original "second messenger" to be discovered. Its formation is promoted by adenylyl cyclase activation after ligation of G protein-coupled receptors by ligands including hormones, autocoids, prostaglandins, and pharmacologic agents. Increases in intracellular cAMP generally suppress innate immune functions, including inflammatory mediator generation and the phagocytosis and killing of microbes. The importance of the host cAMP axis in regulating antimicrobial defense is underscored by the fact that microbes have evolved virulence-enhancing strategies that exploit it. Many clinical situations that predispose to infection are associated with increases in cAMP, and therapeutic strategies to interrupt cAMP generation or actions have immunostimulatory potential. This article reviews the anatomy of the cAMP axis, the mechanisms by which it controls phagocyte immune function, microbial strategies to dysregulate it, and its clinical relevance.

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

“…The immunomodulatory effects of PGE 2 largely result from its ability to increase intracellular cAMP through the stimulatory G protein (G s )-coupled E prostanoid (EP) receptors EP2 and EP4 (8). Increases in intracellular cAMP are transduced into cellular responses via the activation of two downstream effector molecules, cAMP-dependent protein kinase A (PKA) and the exchange protein directly activated by cAMP-1 (Epac-1) (9,10). Specificity in PKA signaling exists at both biochemical and spatial levels.…”

Mimicking tricks from nature with sensory organic–inorganic hybrid materials

“…80,81 These sensing systems are readily prepared through simple formation of self-assembled monolayers (SAMs) on gold electrodes using the well-known spontaneous addition of organosulfur derivatives to Au surfaces to form the corresponding SAMs. For instance, in a representative example, gold electrodes were modified with SAMs of thioctic acid for the detection of protamine using the redox-active species [Ru(NH 3 …”

“…The capping molecules were anchored on the surface through a reaction of previously attached mercaptopropyl groups with a squaraine derivative (vide supra). The uncapping protocol is based on the reaction of the thiophilic CH 3 Hg + with the APC moieties, resulting in the coordination of the cation to the thiol groups and liberation of the SQ chromophore. Employing a straightforward protocol, this method could successfully be used to determine CH 3 Hg + in fish samples.…”

“…The uncapping protocol is based on the reaction of the thiophilic CH 3 Hg + with the APC moieties, resulting in the coordination of the cation to the thiol groups and liberation of the SQ chromophore. Employing a straightforward protocol, this method could successfully be used to determine CH 3 Hg + in fish samples. 105 An inherent feature of such systems is its previously mentioned nature of signal amplification.…”

“…105 An inherent feature of such systems is its previously mentioned nature of signal amplification. For instance, in this particular system reaction of one equivalent of CH 3 Hg + with the APC groups leads to the delivery of an average of 200 safranine O molecules (Fig. 17).…”