Comparative aspects of natriuretic peptide physiology in non-mammalian vertebrates: a review

The natriuretic peptide system is a complex family of peptides and receptors that is primarily linked to the maintenance of osmotic and cardiovascular homeostasis. A natriuretic peptide system is present in each vertebrate class but there are varying degrees of complexity in the system. In agnathans and chondrichthyians, only one natriuretic peptide has been identified, while new data has revealed that multiple types of natriuretic peptides are present in bony fish. However, it seems in tetrapods that there has been a reduction in the number of natriuretic peptide genes, such that only three natriuretic peptides are present in mammals. The peptides act via a family of guanylyl cyclase receptors to generate the second messenger cGMP, which  mediates a range of physiological effects at key targets such as the gills, kidney and the cardiovascular system. This review summarises the current knowledge of the natriuretic peptide system in non-mammalian vertebrates and discusses the physiological actions of the peptides.

The effect of water deprivation on signalling molecules that utilise cGMP in the Spinifex Hopping Mouse Notomys alexis

In mammals the natriuretic and guanylin peptides influence renal and intestinal fluid content and electrolyte transport by binding to and activating guanylyl cyclase (GC) receptors that in turn stimulate production of the intracellular second messenger guanosine 3':5'-cyclic monophospate
(cGMP). However, the role of natriuretic and guanylin peptides in desert mammals is not understood. The spinifex hopping-mouse (Notomys alexis), has a suite of behavioural and physiological mechanisms that permits survival for extended periods without access to free water. Because signalling molecules that generate cGMP are known to promote water excretion, it was predicted that natriuretic and guanylin peptide synthesis would be down regulated in water-deprived N. alexis, and thus reduce the amount of water lost in the urine and faeces. However, in the kidney ANP and GC-A mRNA levels were increased in water-deprived mice, but CNP and GC-B mRNA levels were decreased. Water deprivation increased guanylin and uroguanylin mRNA expression in the distal colon, but it remained unchanged in the kidney and proximal colon. The expression of GC-C mRNA increased in the proximal colon but not in the distal colon. This study shows that water deprivation differentially affects the expression of regulatory molecules that stimulate cGMP producti

Natriuretic peptide guanylyl cyclase receptors in the kidney of the Japanese eel, Anguilla japonica

Natriuretic peptides are linked to osmoregulation, cardiovascular and volume regulation in fishes. The peptides bind to two guanylyl-cyclase-linked receptors, natriuretic peptide receptor-A (NPR-A) and NPR-B, to elicit their effects. Atrial natriuretic peptide (ANP) binds principally to NPR-A, whereas C-type natriuretic peptide (CNP) binds to NPR-B. The teleost kidney has an important role in the maintenance of fluid and electrolyte balance; therefore, the location of NPR-A and NPR-B in the kidney could provide insights into the functions of natriuretic peptides. This study used homologous, affinity purified, polyclonal antibodies to NPR-A and NPR-B to determine their location in the kidney of the Japanese eel, Anguilla japonica. Kidneys from freshwater and seawater acclimated animals were fixed overnight in 4% paraformaldehyde before being paraffin-embedded and immunostained. NPR-A immunoreactivity was found on the apical membrane of proximal tubule 1 and the vascular endothelium including the glomerular capillaries. In contrast, NPR-B immunoreactivity was located on the smooth muscle of blood vessels including the glomerular afferent and efferent arterioles, and on smooth muscle tissue surrounding the collecting ducts. No difference in the distribution of NPR-A and NPR-B was observed between freshwater and seawater kidneys. Immunoreactivity was not observed in any tissue in which the antibodies had been preabsorbed. In addition, there was no difference in NPR-A and NPR-B mRNA expression between freshwater-acclimated and seawater-acclimated eels. These results suggest that, although utilizing the same second messenger system, ANP and CNP act on different targets within the kidney and presumably elicit different effects.

Plant natriuretic peptide active site determination and effects on cGMP and cell volume regulation

Natriuretic peptides (NP) were first identified in animals where they play a role in the regulation of salt and water balance. This regulation is partly mediated by intracellular changes in cyclic GMP (cGMP). NP immunoanalogues occur in many plants and have been isolated, with two NP encoding genes characterised in Arabidopsis thaliana L. (AtPNP-A and AtPNP-B). Part of AtPNP-A contains the region with homology to human atrial (A)NP. We report here on the effects of recombinant AtPNP-A and smaller synthetic peptides within the ANP-homologous region with a view to identifying the biologically active domain of the molecule. Furthermore, we investigated interactions between AtPNP-A and the hormone, abscisic acid (ABA). ABA does not significantly affect Arabidopsis mesophyll protoplast volume regulation, whereas AtPNP-A and synthetic peptides promote water uptake into the protoplasts causing swelling. This effect is promoted by the membrane permeable cGMP analogue, 8-Br-cGMP, and inhibited by guanylate cyclase inhibitors indicating that increases in cGMP are an essential component of the plant natriuretic peptides (PNP) signalling cascade. ABA does not induce cGMP transients and does not affect AtPNP-A dependent cGMP increases, hence the two regulators differ in their second messenger signatures. Interestingly, AtPNP-A significantly delays and reduces the extent of ABA stimulated stomatal closure that is also based on cell volume regulation. We conclude that a complex interplay between observed PNP effects (stomatal opening and protoplast swelling) and ABA is likely to be cell type specific.

Expression of natriuretic peptide receptor mRNA and functional response to atrial natriuretic peptide and C-type natriuretic peptide in rainbow trout (Oncorhynchus mykiss) head kidney leucocytes

The stimulatory effect of vasomodulatory natriuretic peptide hormones on macrophages and peripheral blood leucocytes in mammals is well-established. However, the relationship in lower vertebrates has not been characterised. Expression of atrial natriuretic peptide, ventricular natriuretic peptide and C-type natriuretic peptide-1, and the guanylyl cyclase-linked (GC) natriuretic peptide receptor-A and -B-type receptors (NPR-A and NPR-B, respectively) was determined by PCR from the mRNA of rainbow trout head kidney leucocytes yielding gene fragments with 100% homology to the same respective natriuretic peptide and NPR-A and -B sequences obtained from other rainbow trout tissues. A mixed population of isolated rainbow trout head kidney leucocytes was stimulated in vitro with trout atrial natriuretic peptide (specific NPR-A agonist) and trout C-type natriuretic peptide (NPR-A and -B agonist) as well as the cGMP agonist 8-bromo-cGMP or the GC inhibitor 8-bromo-phenyl-eutheno-cGMP. Respiratory burst was stimulated by trout atrial natriuretic peptide, trout C-type natriuretic peptide-1 and 8-bromo-cGMP in a dose dependant manner with the highest activity as a result of stimulation with trout C-type natriuretic peptide-1 in excess of that achieved by phorbol myristate acetate (PMA). Equimolar concentrations of the inhibitor, inhibited the respiratory burst caused by the natriuretic peptides and 8-bromo-cGMP. The natriuretic peptide receptors on rainbow trout head kidney leucocytes appear to have a stimulatory function with regard to respiratory burst that is activated through a cGMP second messenger pathway and the natriuretic peptides expressed in the head kidney leucocytes may well act in a paracrine/autocrine manner.

Study of the natriuretic peptide hormone system in plants

In this study, both physiological and cellular effects are elicited by natriuretic peptides (NPs), a novel type of plant hormone. It was found that rat ANP (rANP) influenced stomatal opening movement in Tradescantia sp., where a significant increase in stomatal opening was observed in the presence of 1 µM rANP. Furthermore, this effect is mediated by cGMP, a (putative) second messenger of NPs. Two inhibitors of guanylyl cyclase, LY 83583 and methylene blue, inhibited rANP-induced stomatal opening. In contrast, stomatal opening is induced in a concentration dependent manner by the cell permeant cGMP analogue 8-Br-cGMP. In addition it was found, that like in animals, the secondary structure of rANP is essential for rANP responses. Linearised rANP is biologically inactive. Since ANP elicit plant responses, an attempt was made to isolate NP analogues from plants. A protocol for partially purifying NP from plants was developed. It was found that two fractions eluted from an immunoaffinity chromatography column (0.5 M KCI eluted fraction and 0.75 M KCI eluted fraction) were biologically active. The level of cGMP in response to NPs was also tested. It is suggested that the receptor of NP is specific since only 0.75 M KCI eluted fractions increased cGMP levels in Zea mays root stele tissue. rANP did not elicit an effect on cGMP levels in this tissue and LY 83583 did not affect this response. It is therefore argued that a plant specific biologically active NP system is present in the stele and it is predicted that NPs modulate solute movement in this tissue. NPs also influence K⁺, Na⁺ and H⁺ fluxes in Zea mays root stele. Increase in both K⁺ and Na+ uptake were observed after 30 min., while H⁺ flux shifted immediately toward influx in the presence of both 0.5 and 0.75 KCI eluted fractions. Finally, a model is proposed for the effect of NPs on solute movement and its signalling system in plants.

The platelet intracellular calcium response to serotonin and thrombin in patients with panic disorder.

Serotonin is implicated in both the biology of depression and anxiety. The aim of this study was to examine the platelet intracellular calcium response to serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic disorder compared to 14 matched controls. Patients did not show significantly higher baseline platelet intracellular calcium levels and serotonin stimulated levels of intracellular calcium than control subjects. There was a much smaller standard deviation in the control subjects than in the panic patients. The intracellular calcium response to thrombin activation was however greater in panic patients than in control subjects (P<0.001). The failure of this study to find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with the findings of previous challenge studies that found no consistent dysregulation of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless suggests some receptor mediated second messenger changes independent of serotonin in the disorder.

Blunted adenosine A2a receptor function in platelets in patients with major depression.

There is provisional evidence of involvement of adenosine in depression. In this study, the second messenger intracellular calcium response in platelets was measured in patients with major depression and controls using spectrofluorometry. The primary result of this study was a statistically significantly blunted second messenger response to agonist stimulation in the depressed group compared to the control group at the 50 and 100 nM and 1 microM dosage levels. This suggests that dysregulation of the adenosine A2a receptor may be present in depression.

Platelet supersensitivity to thrombin stimulation in depression: a possible mechanism for the association with cardiovascular mortality.

The mortality risk associated with cardiovascular disease is significantly increased in patients with major depression and panic disorder. The mechanism of this phenomenon is unclear. Thrombin is responsible for platelet aggregation and shape change, and it plays a significant role in the development of thromboembolic events. In this study, we examined the platelet second messenger intracellular calcium response to thrombin stimulation in patients with major depression (n = 13), major depression after response to electroconvulsive therapy (ECT; n = 13), subsyndromal depression (n = 16), schizophrenia (n = 15), and control subjects (n = 65). Patients with major depression had significantly higher intracellular calcium responses to thrombin stimulation than control subjects, patients with subsyndromal depression, and patients with schizophrenia (p < 0.05). Electroconvulsive therapy did not significantly change this supersensitivity. This suggests that the platelet response to activation in patients with major depression is supersensitive. This study suggests a possible mechanism for the increased risk of cardiovascular disease that is seen in these two psychiatric disorders. The lack of difference between the control and subsyndromal depression groups appears to validate current diagnostic thresholds in depression. The failure of nonpharmacologic treatment to alter this marker suggests that it may be a trait marker of depression.

Performance of first and second-order sliding mode observers for nonlinear systems

This paper presents a brief study on the design and performance comparison of conventional first-order and super-twisting second-order sliding mode observers for some nonlinear control systems. Estimation accuracy, fast response, chattering effect, peaking phenomenon and robustness are considered for nonlinear ystems under observer-based output feedback control and state feedback control.

Building the second generation of parallel/distributed virtual reality systems

We present the RhoVeR (Rhodes Virtual Reality) system and classify it as a second generation parallel/distributed virtual reality (DVR) system. We discuss the components of the system and thereby demonstrate its support for virtual reality application development, its configurable, parallel and distributed nature, and its synthesis of first generation DVR techniques.

Use of geographical information systems as a tool for predicting fish yield in tropical reservoirs : case study on Sri Lankan reservoirs

Use of geographical information systems (GIS) in inland fisheries has hitherto been essentially restricted to site evaluation for aquaculture development and assessment of limnological changes in time and space in individual water bodies. The present GIS study was conducted on the land-use pattern of the catchments of nine reservoirs in Sri Lanka, for which detailed fishery data, viz. yield, fishing intensity, landing size of major constituent species, together with selected limnological data such as conductivity and chlorophyll-a, were available. Potential statistical relationships (linear, curvilinear, exponential and second-order polynomial) of fish yield (FY, in kg ha−1 yr−1) to different land-use patterns, such as forest cover (FC, in km2) and shrub-land (SL, in km2), either singly, or in combination, and/or the ratio of each land type to reservoir area (RA in km2) and reservoir capacity (RC in km3), were explored. Highly significant relationships were evident between FY to the ratio of SL and/or FC+SL to RA and/or RC. Similarly, the above land-use types to RA and RC ratios were significantly related to limnological features of the reservoirs. The relationships of FY to various parameters obtained in this study were much better correlated than those relationships of FY to limnological and biological parameters used in yield prediction in tropical and temperate lacustrine waters previously.