Although abundant structural plasticity in the form of axonal retraction, neurite extension, and formation of presynaptic varicosities is displayed by photoreceptors after retinal detachment and during genetic and age-related retinal degeneration, the mechanisms involved are mostly unknown. We demonstrated recently that Ca(2+) influx through cGMP-gated channels in cones and voltage-gated L-type...

A cyclic GMP (cGMP) signaling pathway, comprising C-type natriuretic peptide (CNP), its guanylate cyclase receptor Npr2, and cGMP-dependent protein kinase I, is critical for the bifurcation of dorsal root ganglion (DRG) and cranial sensory ganglion axons when entering the mouse spinal cord and the hindbrain respectively. However, the identity and functional relevance of phosphodiesterases (PDEs...

The binding of cGMP to the noncatalytic sites on two isoforms of the phosphodiesterase (PDE) from mammalian rod outer segments has been characterized to evaluate their role in regulating PDE during phototransduction. Nonactivated, membrane-associated PDE (PDE-M, alpha beta gamma2) has one exchangeable site for cGMP binding; endogenous cGMP remains nonexchangeable at the second site. Non-activat...

The present study was designed to determine the capability of human renal proximal tubule (RPT) to generate and export guanosine cyclic 3', 5' monophosphate (cGMP) in response to direct stimulation of soluble guanylyl cyclase by nitric oxide (NO) donors. In addition, we investigated whether cGMP extrusion from human RPT cells is required for inhibition of cellular sodium uptake. RPT cells were ...

Baseline function and signal transduction are depressed in hearts with hypertrophic failure. We tested the hypothesis that the effects of cGMP and its interaction with cAMP would be reduced in cardiac myocytes from hypertrophic failing hearts. Ventricular myocytes were isolated from control dogs, dogs with aortic valve stenosis hypertrophy, and dogs with pacing hypertrophic failure. Myocyte fun...

Recent medical advances suggest that the cellular natriuretic peptide/cGMP and NO/cGMP effector systems represent important signal transduction pathways especially in the cardiovascular system. These pathways also appear to be very interesting targets for the possible prevention of cardiovascular diseases. Exciting candidates for prevention include cGMP-dependent signaling networks initiated by...

Most effects of the signaling molecule nitric oxide (NO) are mediated by the stimulation of NO-sensitive guanylyl cyclase (GC) and the subsequent intracellular increase in cGMP. Two isoforms of NO-sensitive GC have been identified to date that share regulatory properties but differ in their subcellular localization; the more ubiquitously expressed alpha1beta1 heterodimer, and the alpha2beta1 is...

Leptin is a regulator of body weight and affects nitric oxide (NO) production. This study was designed to determine whether the myocardial NO-cGMP signal transduction system was altered in leptin-deficient obese mice. Contractile function, guanylyl cyclase activity, and cGMP-dependent protein phosphorylation were assessed in ventricular myocytes isolated from genetically obese (B6.V-Lepob) and ...

We previously showed that hepatic nitric oxide regulates net hepatic glucose uptake (NHGU), an effect that can be eliminated by inhibiting hepatic soluble guanylate cyclase (sGC), suggesting that the sGC pathway is involved in the regulation of NHGU. The aim of the current study was to determine whether hepatic cyclic guanosine monophosphate (cGMP) reduces NHGU. Studies were performed on consci...

The cyclic nucleotide cGMP has been shown to play important roles in plant development and responses to abiotic and biotic stress. Yet much controversy remains regarding the exact role of this second messenger. Progress in unravelling cGMP function in plants was hampered by laborious and time-consuming methodology to measure changes in cellular [cGMP] but the development of fluorescence-based r...