The contributions of guanylyl cyclases to sensory signaling in the olfactory system have been unclear. Recently, studies of a specialized subpopulation of olfactory sensory neurons (OSNs) located in the main olfactory epithelium have provided important insights into the neuronal function of one receptor guanylyl cyclase, GC-D. Genetargeted mice expressing reporters such as β-galactosidase and g...

The intestinal guanylyl cyclase-C (GC-C) was originally identified as an Escherichia coli heat-stable enterotoxin (STa) receptor. STa stimulates GC-C to much higher activity than the endogenous ligands guanylin and uroguanylin, causing severe diarrhea. To investigate the interactions of the endogenous and bacterial ligands with GC-C, we designed and characterized a soluble and properly folded f...

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...

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...

Folic acid and cAMP are chemoattractants in Dictyostelium discoideum, which bind to different surface receptors. The signal is transduced from the receptors via different G proteins into a common pathway which includes guanylyl cyclase and acto-myosin. To investigate this common pathway, ten mutants which do not react chemotactically to both cAMP and folic acid were isolated with a simple new c...

To understand the molecular mechanisms of cellular stgnalmg of atria1 natrmrettc pepttde (ANP), we have studied Its effect on the enzymatrc activrty of endogenous and overexpressed protein kmase C (PKC) m rat thoracrc aortrc vascular smooth muscle (RTASM) cells Angrotensm II (ANG II), endothelm-1 (ET-l), and 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated fourfold to fivefold PKC acttvny ...

[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 ...