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A business of some heat : molecular imaging of phosphodiesterase 5
Author(s) -
Cumming Paul
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13453
Subject(s) - sildenafil , phosphodiesterase , cgmp specific phosphodiesterase type 5 , cerebrospinal fluid , second messenger system , receptor , positron emission tomography , intracellular , signal transduction , pharmacokinetics , chemistry , pharmacology , medicine , endocrinology , neuroscience , biology , biochemistry , enzyme
G‐protein coupled receptors activate intracellular signaling by well‐known pathways involving cyclic nucleotides or phosphatidylinositol. However, these signaling pathways (second messenger systems) have scarcely been investigated with molecular imaging techniques. This Editorial highlights a preclinical PET study by Gómez‐Vallejo and coworkers, in which the authors studied the cerebral uptake of the prototypic phosphodiesterase 5 (PDE5) inhibitor sildenafil and showed that its action manifested in elevated cGMP levels in cerebrospinal fluid of non‐human primates, but their rat PET studies with [11C]sildenafil failed to show specific binding in brain. This negative PET study underlines that abundance (Bmax) of the target molecule can be decisive for success of a new ligand, and emphasizes the need for further quantitative PET studies of PDE5 as calculations suggest that it might yet be detected with a PET tracer of higher affinity than [11C]sildenafil. Read the highlighted article ‘ Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels ’ on page 403.