Effects
Guanylyl cyclase is found in the retina (RETGC) and modulates phototransduction in rods and cones. It is part of the calcium negative feedback system that is activated in response to light hyperpolarizing the photoreceptors. This causes less intracellular calcium, which stimulates guanylyl cyclase-activating proteins (GCAPs). Studies have shown that cGMP synthesis in cones is about 5-10 times higher than it is in rods, which may play an important role in modulating cone adaption to light. Additionally, studies have also shown that zebrafish express a higher number of GCAP’s than mammals, and that zebrafish GCAPs can bind at least three calcium ions.
Guanylate Cyclase C (GC-C) is an enzyme expressed mainly in intestinal neurons. Activation of GC-C amplifies the excitatory cell response which is modulated by glutamate and acetylcholine receptors. GC-C, while mainly known for its secretory regulation in the intestinal epithelium, is also expressed in the brain. Specifically, it is found in the somata and dendrites of dopaminergic neurons in the ventral tegmental area (VTA) and the substantia nigra. Some studies implicate this pathway as having a role in attention deficiency and hyperactive behavior.
Soluble guanylate cyclase contains a molecule of heme, and is primarily activated by the binding of nitric oxide (NO) to that heme ). sGC is primary receptor for nitric oxide (NO) a gaseous, membrane soluble neurotransmitter. sGC expression has been shown to be highest in the striatum compared to other brain regions and has been explored as a possible candidate for restoring striatal dysfunction in Parkinson’s Disease. sGC acts as an intracellular intermediary for regulating dopamine and glutamate. Upregulation, which creates neuronal sensitivity, of the cGMP in a dopamine depleted striatum has been associated with the symptoms of Parkinson’s. Increased intracellular cGMP has been shown to contribute to excessive neuron excitability and locomotor activity. Activation of this pathway can also stimulate presynpatic glutamate release and cause an upregulation of AMPA receptors postsynaptically
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