atrial-natriuretic-factor and 8-bromoguanosino-3--5--cyclic-monophosphorothioate

Atrial and brain natriuretic peptides (ANP and BNP) exist in the central nervous system and modulate neuronal function, although the locus of actions and physiological mechanisms are still unclear. In the present study we used rat spinal sacral dorsal commissural nucleus (SDCN) and hippocampal 'synaptic bouton' preparations, to record both spontaneous and evoked glycinergic inhibitory postsynaptic currents (sIPSCs and eIPSCs) in SDCN neurons, and the evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA3 neurons. ANP potently and significantly reduced the sIPSC frequency without affecting the amplitude. ANP also potently reduced the eIPSCs amplitude concurrently increasing the failure rate and the paired pulse ratio response. These ANP actions were blocked by anantin, a specific type A natriuretic peptide receptor (NPR-A) antagonist. The results clearly indicate that ANP acts directly on glycinergic presynaptic nerve terminals to inhibit glycine release via presynaptic NPR-A. The ANP effects were not blocked by the membrane permeable cGMP analog (8Br-cGMP) suggesting a transduction mechanisms not simply related to increasing cGMP levels in nerve terminals. BNP did not affect on glycinergic sIPSCs and eIPSCs. Moreover, both ANP and BNP had no effect on glutamatergic EPSCs in hippocampal CA3 neurons. The results indicate a potent and selective presynaptic inhibitory action of ANP on glycinergic transmission in spinal cord sensory circuits.

Topics: 4-Aminopyridine; 6-Cyano-7-nitroquinoxaline-2,3-dione; Anesthetics, Local; Animals; Animals, Newborn; Atrial Natriuretic Factor; Cyclic GMP; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glycine; Hippocampus; Inhibitory Postsynaptic Potentials; Lidocaine; Neurons; Peptides, Cyclic; Potassium Channel Blockers; Presynaptic Terminals; Rats; Rats, Wistar; Spinal Cord; Thionucleotides

In rat hepatocytes, atrial natriuretic peptide (ANP) elevates cGMP through activation of particulate guanylyl cyclase and attenuates Ca(2+) signals by stimulating net plasma membrane Ca(2+) efflux. We show here that ANP-stimulated hepatocyte Ca(2+) efflux is mediated by protein kinase G (PKG) isotype I. Furthermore, we show that ANP recruits endogenous PKGIalpha, but not PKGIbeta, to the plasma membrane. These effects are mimicked by 8-bromo-cGMP, but not by the soluble guanylyl cyclase activators, sodium nitroprusside and YC-1. We propose that ANP, through localized cGMP elevation, promotes plasma membrane recruitment of PKGIalpha, which, in turn, stimulates Ca(2+) efflux.

Topics: Animals; Atrial Natriuretic Factor; Calcium; Cell Membrane; Cyclic GMP; Cyclic GMP-Dependent Protein Kinase Type I; Cyclic GMP-Dependent Protein Kinases; Hepatocytes; Indazoles; Male; Nitroprusside; Rats; Rats, Wistar; Thionucleotides

C-type natriuretic peptide (CNP) is the major natriuretic peptide in the brain and its mRNA has been reported in the central nervous system, which supports local synthesis and its role as a neuromodulator. The aim of the present work was to study the effect of centrally applied CNP on pancreatic secretion. Rats were fitted with a lateral cerebroventricular cannula one-week before secretion studies. The central administration of CNP dose-dependently enhanced pancreatic fluid and protein output. CNP response was diminished by atropine and hexamethonium, but it was abolished by vagotomy. Neither adrenergic antagonists nor the administration of (D-p-Cl-Phe(6),Leu(17))-vasoactive intestinal peptide (VIP antagonist) or N(omega) Nitro-L arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) affected CNP response. The effect induced by CNP was mimicked by 8-Br-cGMP but not by c-ANP-(4-23) amide (selective agonist of the natriuretic peptide receptor C). Furthermore, CNP interacted with cholecystokinin (CCK) and secretin in the brain to modify pancreatic secretion. Present findings show that centrally applied CNP enhanced pancreatic secretion through a vagal pathway and suggest that CNP response is mediated by the activation of natriuretic peptide guanylyl cyclase coupled receptors in the brain.

Topics: Animals; Atrial Natriuretic Factor; Atropine; Brain; Cyclic GMP; Drug Interactions; Enzyme Inhibitors; Ganglionic Blockers; Hexamethonium; Natriuretic Peptide, C-Type; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pancreas; Parasympatholytics; Peptide Fragments; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Secretin; Sincalide; Thionucleotides; Time Factors; Vagotomy; Vagus Nerve; Vasoactive Intestinal Peptide

Maximal relaxation of airway smooth muscle (ASM) in response to atrial natriuretic peptide (ANP), which stimulates particulate guanylyl cyclase (pGC), is less than that produced by nitric oxide (NO) and other compounds that stimulate soluble guanylyl cyclase (sGC). We hypothesized that stimulation of pGC relaxes ASM only by decreasing intracellular Ca(2+) concentration ([Ca(2+)](i)), whereas stimulation of sGC decreases both [Ca(2+)](i) and the force developed for a given [Ca(2+)](i) (i.e., the Ca(2+) sensitivity) during muscarinic stimulation. We measured the relationship between force and [Ca(2+)](i) (using fura 2) under control conditions (using diltiazem to change [Ca(2+)](i)) and during exposure to ANP, diethylamine-NO (DEA-NO), sodium nitroprusside (SNP), and the Sp diastereoisomer of beta-phenyl-1,N(2)-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate (Sp-8-Br-PET-cGMPS), a cell-permeant analog of cGMP. Addition of DEA-NO, SNP, or Sp-8-Br-PET-cGMPS decreased both [Ca(2+)](i) and force, causing a significant rightward shift of the force-[Ca(2+)](i) relationship. In contrast, with ANP exposure, the force-[Ca(2+)](i) relationship was identical to control, such that ANP produced relaxation solely by decreasing [Ca(2+)](i). Thus, during muscarinic stimulation, stimulation of pGC relaxes ASM exclusively by decreasing [Ca(2+)](i), whereas stimulation of sGC decreases both [Ca(2+)](i) and Ca(2+) sensitivity.

Topics: Animals; Atrial Natriuretic Factor; Calcium; Cyclic GMP; Enzyme Activation; Female; Guanylate Cyclase; In Vitro Techniques; Isometric Contraction; Male; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Nitric Oxide Donors; Respiratory System; Spectrometry, Fluorescence; Swine; Thionucleotides; Trachea; Vasodilator Agents

Recent evidence suggests that in plants, as in vertebrates, natriuretic peptides (NPs) regulate homeostasis. In this study noninvasive ion-selective vibrating microelectrodes were used to measure net fluxes of K+, Na+, and H+ in Zea mays root conductive tissue. Immunoreactant plant natriuretic peptides (irPNP) cause immediate net H+ influx and delayed net K+ and Na+ uptake. Delayed net K+ influx was also observed in response to 8-Br-cGMP, however, not accompanied by significant changes in net H+ fluxes. Furthermore, 8-Br-cGMP does not stimulate the plasma membrane H+-ATPase implying that cGMP directly affects cation channels. The data are consistent with NP and cGMP-dependent stimulation of nonselective cation channels with P(K) > P(Na) and point to a complex role for NPs in plant homeostasis.

Topics: Affinity Labels; Animals; Atrial Natriuretic Factor; Cations, Monovalent; Cyclic GMP; Electrophoresis, Polyacrylamide Gel; Hydrogen; Immunoblotting; Models, Biological; Peptides; Plant Proteins; Plant Roots; Potassium; Rats; Sodium; Thionucleotides; Zea mays