Editing Cyclic nucleotide (section)

==History==
The understanding of the concept of second messengers, and in particular the role of cyclic nucleotides and their ability to relay physiological signals to a [[cell (biology)|cell]], has its origins in the research of [[glycogen]] metabolism by [[Carl Ferdinand Cori|Carl]] and [[Gerty Cori]], for which they were awarded a [[Nobel Prize in Physiology or Medicine]] in 1947.<ref name=beavo />  A number of incremental but important discoveries through the 1950s added to their research, primarily focusing on the activity of [[glycogen phosphorylase]] in dog [[liver]].  Glycogen phosphorylase catalyzes the first step in [[glycogenolysis]], the process of breaking [[glycogen]] into its substituent [[glucose]] parts.<ref name=newton />  [[Earl Wilbur Sutherland, Jr.|Earl Sutherland]] investigated the effect of the hormones [[epinephrine|adrenaline]] and [[glucagon]] on glycogen phosphorylase, earning him the Nobel Prize in Physiology or Medicine in 1971.<ref name=beavo />

In 1956 [[Edwin G. Krebs|Edwin Krebs]] and [[Edmond H. Fischer|Edmond Fischer]] discovered that [[adenosine triphosphate]] (ATP) is required for the conversion of [[phosphorylase|glycogen phosphorylase]] b to glycogen phosphorylase a. While investigating the action of adrenaline on [[glycogenolysis]] the next year, Sutherland and Walter Wosilait reported that inorganic phosphate is released when the [[enzyme substrate (biology)|enzyme]] liver phosphorylase is inactivated; but when it is activated, it incorporates a phosphate.<ref name=beavo /> The “active factor” that the hormones produced<ref name=newton />  was finally purified in 1958, and then identified as containing a [[ribose]], a phosphate, and an [[adenine]] in equal ratios. Further, it was proved that this factor reverted to 5’-AMP when it was inactivated.<ref name=beavo />

Evgeny Fesenko, Stanislav Kolesnikov, and Arkady Lyubarsky discovered in 1985 that [[cyclic guanosine monophosphate]] (cGMP) can initiate the photoresponse in [[rod cell|rods]]. Soon after, the role of cNMP in gated ion channels of chemosensitive [[cilium|cilia]] of [[olfactory sensory neuron]]s was reported by Tadashi Nakamura and Geoffrey Gold. In 1992 Lawrence Haynes and King-Wai Yau uncovered cNMP’s role in the light-dependent cyclic-nucleotide-gated channel of [[cone cell|cone photoreceptors]].<ref name=kaupp /> By the end of the decade, the presence of two types of intramembrane receptors was understood: Rs (which stimulates [[cyclase]]) and Ri (which inhibits cyclase).  Wei-Jen Tang and James Hurley reported in 1998 that adenylyl cyclase, which synthesizes cAMP, is regulated not only by [[hormone]]s and [[neurotransmitter]]s, but also by [[phosphorylation]], [[calcium]], [[forskolin]], and guanine nucleotide-binding proteins ([[G proteins]]).<ref name=newton />