Guanylate cyclase pathway

Multicomponent Hormonal Systems Facilitate a Great Variety of Responses The Guanylate Cyclase Pathway Calcium and the Inositol Trisphosphate Pathway Steroid Receptors Modulate the Rate of Transcription... 

It is of interest that in all patients there was a rise in plasma cGMP levels in the superior vena cava and systemic arterial blood from 10 2 to 53 14 pmol/ml (P < 0.05) following inhaled nitric oxide. This suggests that the nitric oxide was effectively delivered to the pulmonary vascular bed and that there was no impediment in the pulmonary guanylate cyclase pathway that impaired response. 

Guanylate cyclase signaling pathway also utilizes an enzyme-linked receptor model. The effector enzyme, guanylate cyclase, converts GTP to cGMP, which in turn activates cGMP dependent protein kinase or phosphodiesterases. 

A special guanylate cyclase receptor can be found in the nitric oxide (NO) signaling pathway. The activation of the sequence of events in that pathway results in smooth muscle relaxation. This pathway is directly linked to other cascades by receiving a Ca2+ signal and utilizing calmodulin (CaM) as transmitter protein. 

Diacylglycerol, on the other hand, is lipid soluble and remains in the lipid bilayer of the membrane. There it can activate protein kinase C (PKC), a very important and widely distributed enzyme which serves many systems through phosphorylation, including neurotransmitters (acetylcholine, a,- and P-adrenoceptors, serotonin), peptide hormones (insulin, epidermal growth hormone, somatomedin), and various cellular functions (glycogen metabolism, muscle activity, structural proteins, etc.), and also interacts with guanylate cyclase. In addition to diacylglycerol, another normal membrane lipid, phos-phatidylserine, is needed for activation of PKC. The DG-IP3 limbs of the pathway usually proceed simultaneously. 

This review will focus on three main reactions of dilute nitric oxide in physiological solutions. The first reaction is the binding of nitric oxide to ferrous heme iron of guanylate cyclase or other proteins, which is important for the activation of signal transduction pathways. 

Denninger JW, Marietta MA. Guanylate cyclase and the NO/cGMP signalling pathway. Biochem Biophys Acta 1999 1411 334. 

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