It has been suggested that nitric oxide (NO) stimulates the cyclooxygenase (COX)-dependent mechanisms in the ocular vasculature; however, the importance of the pathway in regulating retinal circulation in vivo remains to be elucidated. Therefore, we investigated the role of COX-dependent mechanisms in NO-induced vasodilation of retinal blood vessels in thiobutabarbital-anesthetized rats with an...

[Type abstract text here.] Nerve-induced release of nitric oxide LIST OF PUBLICATIONS The present thesis is based on the following papers, which will be referred to by their Roman numerals. I OLGART, C., HALLÉN, K., WIKLUND, N.P., IVERSEN, H.H. & GUSTAFSSON, L.E. (1998). Blockade of nitrergic neuroeffector transmission in guinea-pig colon by a selective inhibitor of soluble guanylyl cyclase. Ac...

The mechanisms of proguanylin synthesis and secretion in the intestine are incompletely understood. We designed an in vitro model to study proguanylin secretion in a model of intestinal villous epithelial cells. The C2/bbe1 cell line, a differentiated subclone of Caco-2 cells, was used to examine the direction of proguanylin secretion and the potential for feedback regulation via activators of ...

The peptide hormones uroguanylin and guanylin have been traditionally thought to be mediators of fluid-ion homeostasis in the vertebrate intestine. They serve as ligands for receptor guanylyl cyclase C (GC-C), and both receptor and ligands are expressed predominantly in the intestine. Ligand binding to GC-C results in increased cyclic GMP production in the cell which governs downstream signalin...

In a number of isolated blood vessel types, hypoxia causes an acute contraction that is dependent on the presence of nitric oxide and activation of soluble guanylyl cyclase. It is more pronounced when the preparations are constricted and is therefore termed hypoxic augmentation of vasoconstriction. This hypoxic response is accompanied by increases in the intracellular level of inosine 5'-tripho...

Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme carrying a heme prosthetic group that functions as a nitric oxide (NO) sensor. sGC is present in most cells types, including the vascular endothelium, where its biological functions remain largely unexplored. Herein, we have investigated the role of sGC in angiogenesis and angiogenesis-related properties of endothelial cells (EC). Initi...

Substantial guanylyl cyclase activity was detected in membrane fractions prepared from Caenorhabditis elegans (100 pmol cGMP/min/mg at 20 degrees C or 500 pmol cGMP/min/mg at 37 degrees C), suggesting the potential existence of orphan cyclase receptors in the nematode. Using degenerate primers, a cDNA clone encoding a putative membrane form of the enzyme (GCY-X1) was obtained. The apparent cycl...

Guanylyl cyclase activating proteins (GCAPs) are calcium/magnesium binding proteins within neuronal calcium sensor proteins group (NCS) of the EF-hand proteins superfamily. GCAPs activate retinal guanylyl cyclase (RetGC) in vertebrate photoreceptors in response to light-dependent fall of the intracellular free Ca(2+) concentrations. GCAPs consist of four EF-hand domains and contain N-terminal f...

Background Post translational modifications regulate several signalling pathways and glycosylation is emerging as a key player in this regulatory process. Glycosylation of cell surface receptors modulate the downstream signalling pathway and when altered causes a change in the normal physiology of the cell [1]. Guanylyl cyclase C (GC-C) belongs to a group of membrane bound receptors that produc...

In Dictyostelium discoideum extracellular cAMP induces chemotaxis via a transmembrane signal transduction cascade consisting of surface cAMP receptors, G-proteins and effector enzymes including adenylyl cyclase, guanylyl cyclase and phospholipase C. Previously it was demonstrated that some cAMP derivatives such as 3'-deoxy-3'-aminoadenosine 3':5'-monophosphate (3'NH-cAMP) bind to the receptor a...