Neuronal circuits are shaped during development by the coordinated action of guidance factors and signals that regulate axonal branching. Unlike guidance cues, the molecules and signaling cascades that underlie axonal branching remain to be resolved. Here we show that the secreted molecule C-type natriuretic peptide (CNP) induces a cGMP signaling cascade via its receptor particulate guanylyl cy...

Most of the effects of the signaling molecule nitric oxide (NO) are mediated by cGMP, which is synthesized by soluble guanylyl cyclase and degraded by phosphodiesterases. Here we show that in platelets and aortic tissue, NO led to a biphasic response characterized by a tremendous increase in cGMP (up to 100-fold) in less than 30 s and a rapid decline, reflecting the tightly controlled balance o...

The membrane and soluble guanylyl cyclases (sGCs) are key families of enzymes that produce the second messenger cGMP. Although both families recognize different ligands and have therefore different N-terminal input domains, they do have similar C-terminal output domains containing a coiled-coil domain and a guanylyl cyclase catalytic domain. We present here our latest structure-function studies...

No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary arter...

In primary cultures of rat cerebellar granule cells with a functional network of glutamatergic neurons, the expression pattern of the different subunits of nitric-oxide (NO)-sensitive guanylyl cyclase changes during cell differentiation. These cells express the alpha1, alpha2 and beta1 subunits of NO-sensitive guanylyl cyclase and synthesize cyclic guanosine monophosphate (cGMP) in response to ...

Although plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated early after myocardial infarction (MI), the significance is not fully understood. We therefore investigated the function of natriuretic peptides after induction of MI in knockout (KO) mice lacking the natriuretic peptide receptor guanylyl cyclase-A, the receptor for ANP and BNP. KO and wi...

OBJECTIVE Platelet activation significantly contributes to cardiovascular morbidity and mortality in diabetes. An association between impaired NO-mediated platelet inhibition and platelet activation has recently been demonstrated in experimental diabetes. Guanylyl cyclase activation enhances the reduced signaling via the NO/cGMP pathway. We investigated whether chronic guanylyl cyclase activati...