|
| ||
|
|
||
C-type Natriuretic Peptide (c-type + natriuretic_peptide)
Selected AbstractsC-type natriuretic peptide (CNP) regulates cocaine-induced dopamine increase and immediate early gene expression in rat brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Nathalie Thiriet Abstract The neuropeptide C-type natriuretic peptide (CNP) is the primary biologically active natriuretic peptide in brain. Using in situ hybridization, the present report demonstrates that CNP regulates egr-1, c-fos and junB immediate early gene expression in rat brain. In the frontal cortex, CNP induced immediate early gene expression whereas it inhibited dose-dependently the cocaine-induced early gene expression in the dopaminergic projection fields nucleus accumbens and caudate,putamen. CNP may produce its effect directly on dopaminergic neurons because we found that its receptor, guanylyl cyclase GC-B, was expressed in the mesencephalon where dopaminergic neurons originate, as well as in their projection fields. The inhibition by CNP of the early gene expression elicited by cocaine in the caudate,putamen is correlated with a CNP-evoked decrease in cocaine-induced rise in extracellular dopamine, measured by in vivo microdialysis experiments. The significance of the inhibition of cocaine-induced dopamine release and early gene induction by the endogenous peptide CNP is demonstrated by data indicating that CNP reduced the cocaine-induced spontaneous locomotor activation. By inhibiting dopaminergic neuronal activity, CNP represents a potential negative regulator of related behavioural effects of cocaine. [source] Nitric Oxide-Sensitive Guanylyl Cyclase Activity Inhibition Through Cyclic GMP-Dependent DephosphorylationJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Rut Ferrero Abstract: The soluble form of guanylyl cyclase (sGC) plays a pivotal role in the transduction of inter- and intracellular signals conveyed by nitric oxide. Here, a feedback inhibitory mechanism triggered by cyclic guanosine-3,,5,-monophosphate (cGMP)-dependent protein kinase (PKG) activation is described. Preincubation of chromaffin cells with C-type natriuretic peptide, which increased cGMP levels and activated PKG, or with cGMP-permeant analogue (which also activates PKG), in the presence of a broad-spectrum phosphodiesterase inhibitor, resulted in a decrease in subsequent sodium nitroprusside (SNP)-dependent cGMP elevations. This inhibitory effect was mimicked by activating a protein phosphatase and counteracted by the selective PKG inhibitor KT-5823 and by different protein phosphatase inhibitors. Immunoprecipitation of sGC from cells submitted to different treatments followed by immunodetection with antiphosphoserine antibodies (clone 4A9) showed changes in phosphorylation levels of the , subunit of sGC, and these changes correlated well with differences in SNP-elicited cGMP accumulations. Pretreatment of cells with several PKG inhibitors or protein phosphatase inhibitors produced an enhancement of SNP-stimulated cGMP rises without changing the SNP concentration required to produce half-maximal or maximal responses. Taken together, these results indicate that the catalytic activity of sGC is closely coupled to the phosphorylation state of its , subunit and that the tonic activity of PKG or its stimulation regulates sGC activity through dephosphorylation of the , subunit. [source] Effects of Natriuretic Peptides on Intracavernous Pressure and Blood Pressure in Conscious RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2008Naoki Aizawa PhD ABSTRACT Introduction., Natriuretic peptides activate particulate guanylyl cyclases and have been shown to induce penile erection in rats, rabbits, and humans. Aim., We investigated the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) on intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious, free-moving rats. Methods., ICP and BP were measured in male Sprague,Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Natriuretic peptides were given by intravenous bolus (3, 10, and 30 nmol/kg) or continuous (0.1 and 1 nmol/kg/minute) administration. Main Outcome Measures., The number of animals with increases in ICP were determined. Amplitudes and durations of ICP responses and changes in BP were also evaluated. Results., More animals had multiple transient increases of ICP in response to ANP and BNP than to CNP. The increases in ICP were transient and appeared to be an "all or none" response. ANP and BNP decreased BP more than CNP, especially with bolus administration. Conclusions., These findings show that in rats, erectile responses can be initiated by ANP, BNP, and less effectively, by CNP. ANP and BNP have a high affinity for the natriuretic peptide receptor-A, suggesting that this receptor is involved in the responses. Aizawa N, Ishizuka O, Ogawa T, Mizusawa H, Igawa Y, Nishizawa O, and Andersson K-E. Effects of natriuretic peptides on intracavernous pressure and blood pressure in conscious rats. J Sex Med 2008;5:2312,2317. [source] C-type natriuretic peptide in prostate cancerAPMIS, Issue 1 2009SOEREN JUNGE NIELSEN C-type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N-terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, proCNP-derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N-terminal proCNP, proCNP (1,50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP-22 and N-terminal proCNP. Tissue extracts from human prostate cancer contained mostly N-terminal proCNP [median 5.3 pmol/g tissue (range 1.0,12.9)] and less CNP [0.14 pmol/g tissue (0.01,1.34)]. Immunohistochemistry demonstrated the presence of the peptides in prostatic epithelial cells. The N-terminal proCNP concentrations in plasma were marginally lower in patients with localized prostate cancer compared with control subjects [13.8 pmol/l (11.0,17.2) vs. 15.1 pmol/l (10.4,23.2), p=0.002] but not enough to justify the use of N-terminal proCNP as a cancer marker. Further research is needed to establish whether measurement of proCNP-derived peptides may offer clinical information. [source] Ion channel formation and membrane-linked pathologies of misfolded hydrophobic proteins: The role of dangerous unchaperoned moleculesCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2002Joseph I Kourie Summary 1.,Protein,membrane interaction includes the interaction of proteins with intrinsic receptors and ion transport pathways and with membrane lipids. Several hypothetical interaction models have been reported for peptide-induced membrane destabilization, including hydrophobic clustering, electrostatic interaction, electrostatic followed by hydrophobic interaction, wedge × type incorporation and hydrophobic mismatch. 2.,The present review focuses on the hypothesis of protein interaction with lipid membranes of those unchaperoned positively charged and misfolded proteins that have hydrophobic regions. We advance the hypothesis that protein misfolding that leads to the exposure of hydrophobic regions of proteins renders them potentially cytotoxic. Such proteins include prion, amyloid , protein (A,P), amylin, calcitonin, serum amyloid and C-type natriuretic peptides. These proteins have the ability to interact with lipid membranes, thereby inducing membrane damage and cell malfunction. 3.,We propose that the most significant mechanism of membrane damage induced by hydrophobic misfolded proteins is mediated via the formation of ion channels. The hydrophobicity based toxicity of several proteins linked to neurodegenerative pathologies is similar to those observed for antibacterial toxins and viral proteins. 4.,It is hypothesized that the membrane damage induced by amyloids, antibacterial toxins and viral proteins represents a common mechanism for cell malfunction, which underlies the associated pathologies and cytotoxicity of such proteins. [source] | |||||||||||||