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Cyclic guanosine monophosphate, usually abbreviated cGMP in physiological contexts, is a nucleotide whose phosphate links the 3′ and 5′ positions of its ribose in an intramolecular ring. It acts as a second messenger: changes in its concentration connect upstream activity to downstream targets. Its cyclic phosphate arrangement distinguishes it from ordinary linear guanosine monophosphate.

Guanylate cyclase produces cGMP from guanosine triphosphate, while a suitable phosphodiesterase hydrolyzes the cyclic linkage. The number of phosphate groups is not the central distinction between cyclic and linear GMP: both names describe one phosphate, with different bonding arrangements.

A classic experiment tested how this messenger affects a membrane directly. In excised inside-out patches from rod outer-segment membranes, cGMP applied to the inner face reversibly increased cationic conductance. The effect occurred without nucleoside triphosphates, arguing against mediation by protein phosphorylation in that assay. Cyclic AMP and 2′,3′-cyclic GMP did not reproduce the response under the reported tests.^[ref]

The result makes molecular recognition concrete: related cyclic nucleotides are not automatically interchangeable. In the visual pathway, activated transducin can stimulate downstream phosphodiesterase activity, connecting rhodopsin activation with a change in the messenger system.^[ref]

A concentration measurement and a channel response nevertheless answer different questions. To interpret a signaling experiment, specify the compartment, time and target; a single whole-cell average need not capture the concentration experienced by every molecular partner.

E. E. Fesenko is the first author of a 1985 experiment showing that cyclic guanosine monophosphate can directly increase electrical conductance in membrane patches from rod cells. The original publisher gives the byline Evgeniy E. Fesenko; the initial-only article title is retained.^[ref]

The investigators excised inside-out membrane patches and applied cyclic guanosine monophosphate to the exposed inner face. Conductance increased reversibly even without nucleoside triphosphates, arguing against a requirement for an intervening phosphorylation reaction in that preparation. Related tested nucleotides did not reproduce the effect.^[ref]

Excising a patch simplified the experiment: an electrical response could be tested without the entire photoreceptor remaining intact. It supported a membrane-local action of the signal, while leaving the complete light-response sequence in a living rod cell as a further question.